Mice homozygous for the recessive NIH allele of the Niemann Pick type C1 gene (Npc1^m1N) show a dual deficiency of sphingomyelinase and glucocerebrosidase activity. The overall phenotype resembles the sphingomyelinosis condition seen in mice homozygous for the sphingomyelinosis allele (Npc1^spm, Stock No. 002760). Sphingomyelinosis mutant mice begin to lose weight and to show tremor and ataxic gait at about 7 weeks of age. Weight loss continues and tremor and ataxia become more severe until death at about 12 to 14 weeks of age. The liver and spleen are also enlarged and Purkinje cells in the cerebellum are severely depleted. Sphingomyelin and free cholesterol are markedly elevated in liver and spleen but not in brain. Sphingomyelinosis closely resembles that of human Niemann-Pick Type C disease patients.

The mutant allele consists of 824 bp of MaLR retroposon-like DNA which replaced 703 bp of wild-type genomic sequence spanning 44 bp of an exon and 659 bp of the downstream intron. A truncated gene product (mRNA) is detected by Northern blot analysis of liver and brain tissue from homozygous mice. No protein is detected by Western blot analysis of liver from homozygotes.

Development

This mutation arose on the BALB/cNctr inbred background at the National Center for Toxicology Research (Jefferson, Arkansas) in 1975. The mutant allele consists of 824 bp of MaLR retroposon-like DNA which replaced 703 bp of wild-type genomic sequence. The mice were transferred to The Jackson Laboratory in 1982 from Dr. William Pavan (NIH).

Control Suggestions

Wild-type from the colony

Additional Information

Considerations for Choosing Controls

Genetics

Npc1^m1N

Allele Symbol: Npc1^m1N

Allele Name	Niemann Pick type C1 NIH
Allele Type	Spontaneous
Allele Synonym(s)	-^npc; CSD; NPC; NPC1; NPC1-; Npc-; Npc1^N; lcsd; lysosomal cholesterol storage disease; nctr; npc1^NIH; npc^nih
Gene Symbol and Name	Npc1, NPC intracellular cholesterol transporter 1
Gene Synonym(s)	A430089E03Rik; A430089E03Rik; C85354; C85354; Cdig2; D18Ertd139e; D18Ertd139e; D18Ertd723e; D18Ertd723e; DNA segment, Chr 18, ERATO Doi 139, expressed; DNA segment, Chr 18, ERATO Doi 723, expressed; NPC; Niemann-Pick type C1; RIKEN cDNA A430089E03 gene; SLC66A1; expressed sequence C85354; lcsd; lcsd; lysosomal cholesterol storage disease; neuroscience mutagenesis facility, 164; nmf164; nmf164; sphingomyelinosis; spm
Strain of Origin	BALB/c
Chromosome	18
Molecular Note	824 bp of MaLR retroposon-like DNA replaced 703 bp of wild-type genomic sequence spanning 44 bp of an exon and 659 bp of the downstream intron. The insertion results in premature truncation of the protein deleting 11 out of 13 transmembrane domains. Northern blot analysis revealed marked decrease in gene expression in liver and brain from homozygous mutant animals.

Disease/Phenotype

Disease Terms

Research Areas By Genotype

This mouse can be used to support research in many areas including:

Internal/Organ Research
- Liver Defects
- Spleen Defects
Metabolism Research
Neurobiology Research
- Ataxia (Movement) Defects
- Cerebellar Defects
- Metabolic Defects
- Myelination Defects
- Neurodegeneration
- Neuromuscular defects
- Tremor Defects
Research Tools
- Metabolism Research

Genotype: Npc1^m1N related

Internal/Organ Research
- Liver Defects
- Spleen Defects
Metabolism Research
Neurobiology Research
- Ataxia (Movement) Defects
- Cerebellar Defects
- Metabolic Defects
- Myelination Defects
- Neurodegeneration
- Neuromuscular defects
- Tremor Defects

Mammalian Phenotype Terms by Genotype

Genotype: Npc1^m1N/Npc1^m1N
BALB/c-Npc1^m1N

mortality/aging

premature death
- average lifespan of approximately 80 days
- mutants start to die at 73 days of age

growth/size/body region phenotype

weight loss
- mutants exhibit a progressive weight loss from 4 weeks of age

nervous system phenotype

Purkinje cell degeneration
- degree of loss is more severe at P63 than in Npc1^tm1.1Dso homozygotes
- lower number of surviving Purkinje cells in cerebellar lobes VIII and X
- progressive, age-dependent Purkinje cell degeneration

abnormal Purkinje cell morphology
- polymembranous storage bodies are found in lobule X Purkinje cells from P63 mice

abnormal microglial cell activation
- age dependent increase in microglial activity
- progression and spatial pattern is more advanced in comparison to Npc1^tm1.1Dso homozygotes

astrocytosis
- age dependent increase in astrocyte reactivity
- increase in astrocytosis and microglia activation
- progression and spatial pattern is more advanced in comparison to Npc1^tm1.1Dso homozygotes

decreased brain size

demyelination
- mutants exhibit demyelination in the white matter

increased brain cholesterol level
- Background Sensitivity - decreased accumulation in P49 liver tissue as compared to C57BL/6 background, but level is higher than control
- cholesterol accumulation within cell bodies and axonal segments of neocortical neurons
- mutants exhibit vesicular accumulation of cholesterol in the cerebellum
- subcellular storage of cholesterol in lobule X Purkinje neurons in P63 mice

behavior/neurological phenotype

impaired coordination
- progressive decline in motor coordination after 4 weeks of age

homeostasis/metabolism phenotype

abnormal ceramide level
- Background Sensitivity - decreased accumulation in P49 liver tissue as compared to C57BL/6 background

abnormal ganglioside level
- GM2 and GM3 ganglioside accumulation is higher than in Npc1^tm1.1Dso homozygotes
- GM2 ganglioside accumulation within cell bodies and axonal segments of neocortical neurons
- subcellular storage of ganglioside GM2 in lobule X Purkinje neurons in P63 mice

abnormal lipid homeostasis

abnormal lipid level
- Background Sensitivity - decreased lipid accumulation in P49 liver tissue as compared to C57BL/6 background
- lipids include: ceramides, monohexosyceramides, sphingomyelins, sphingoid bases, gangiosides, free cholesterol, 24(S)-hydroxycholesterol, 4beta-hydroxy cholesterol and cholesterol ester

abnormal sphingomyelin level
- Background Sensitivity - decreased accumulation in P49 liver tissue as compared to C57BL/6 background

increased brain cholesterol level
- Background Sensitivity - decreased accumulation in P49 liver tissue as compared to C57BL/6 background, but level is higher than control
- cholesterol accumulation within cell bodies and axonal segments of neocortical neurons
- mutants exhibit vesicular accumulation of cholesterol in the cerebellum
- subcellular storage of cholesterol in lobule X Purkinje neurons in P63 mice

increased liver cholesterol level
- cholesterol accumulation in hepatocytes and liver macrophages

cellular phenotype

increased macrophage derived foam cell number
- liver macrophages exhibit a progressive foamy transformation

hematopoietic system phenotype

abnormal macrophage morphology
- polymembranous storage bodies found in liver macrophages and hepatocytes

abnormal microglial cell activation
- age dependent increase in microglial activity
- progression and spatial pattern is more advanced in comparison to Npc1^tm1.1Dso homozygotes

increased macrophage derived foam cell number
- liver macrophages exhibit a progressive foamy transformation

immune system phenotype

abnormal macrophage morphology
- polymembranous storage bodies found in liver macrophages and hepatocytes

abnormal microglial cell activation
- age dependent increase in microglial activity
- progression and spatial pattern is more advanced in comparison to Npc1^tm1.1Dso homozygotes

increased macrophage derived foam cell number
- liver macrophages exhibit a progressive foamy transformation

liver/biliary system phenotype

abnormal hepatocyte morphology
- polymembranous storage bodies found in liver macrophages and hepatocytes

increased liver cholesterol level
- cholesterol accumulation in hepatocytes and liver macrophages

Genotype: Npc1^m1N/Npc1^m1N
involves: BALB/c

mortality/aging

premature death
- mice die between 80 and 100 days of age from neurodegenerative disease
- ~75 day life span

nervous system phenotype

Purkinje cell degeneration
- localized axonal swellings, malformations of the dendritic arbor, and accumulation of vesicular storage materials within the cytoplasm

abnormal CNS glial cell morphology
- glial cells in the corpus callosum reduced by 52%

abnormal Purkinje cell morphology
- axonal swelling by 11 weeks of age

abnormal adenohypophysis morphology
- the mutant anterior pituitary displays vacuolated cells, suggestiing low rates of feedback control and increased hormone synthesis and secretion

abnormal cerebellum anterior vermis morphology
- by P45, Purkinje cell loss was most evident in the anterior cerebellar vermis
- degenerating cells belonged preferentially to the zebrin II-negative subtype

abnormal cerebellum posterior vermis morphology
- at P60, most surviving Purkinje cells were located in the posterior vermis
- by P45, some Purkinje cell loss was evident in the posterior cerebellar vermis

abnormal myelination
- reduced levels of both myelin protein and myelin cholesterol

abnormal neuron morphology
- vacuolated cytoplasmic storage material in all regions of the central nervous system

adenohypophysis hypoplasia
- the mutant anterior pituitary is hypoplastic relative to wild-type

decreased Purkinje cell number
- earliest cell loss at P45 throughout the cerebellum; cell loss was profound by P60 in the anterior lobe of the cerebellum; no marked loss after P75
- reduction in numbers increases with age
- small reduction in Purkinje cell numbers in the cerebellar hemispheres at 3 weeks of age

decreased brain cholesterol level
- decreased levels in the brain at 7 weeks of age relative to controls
- mice have decreased levels of total cholesterol in the brain

decreased brain weight
- brain weight is lower than in controls mice
- progressive decrease in brain weight, beginning at 7 weeks of age

decreased corpus callosum size
- glial cells reduced by 52%
- reduced in size by 50% at 11 weeks of age

decreased lactotroph cell number
- however, chronic (4-week) treatment with 17beta-estradiol (E2) restores pituitary volume and acidophil numbers to wild-type levels
- the mutant anterior pituitary shows a dramatic reduction in acidophil cell number relative to wild-type

small cerebellum
- cerebellum weight is smaller than controls

cellular phenotype

abnormal cellular cholesterol metabolism
- higher rate of turnover although whole body pool is considerably elevated
- rate of cholesterol synthesis is reduced

abnormal sperm head morphology
- at 60 days of age, aberrant cauda sperm heads are frequentyly observed

absent sperm flagellum
- at 60 days of age, tailless sperm heads are frequently observed

absent sperm head
- at 60 days of age, headless sperm tails are frequently observed

impaired acrosome reaction
- in vitro, mutant sperm are able to bind to zona-free eggs as well as wild-type sperm but fail to fuse with the egg plasma membrane
- interestingly, 30% of total cyritestin protein is not proteolytically processed on mutant cauda sperm, whereas fertilin beta is processed normally
- when zona-intact eggs are used, the in vitro capacity of mutant sperm to bind to the egg zona pellucida is only 14% of the level in wild-type sperm

oligozoospermia
- at 60 days of age, the total number of mutant cauda sperm is reduced to only ~28% of that in wild-type males

teratozoospermia
- at 60 days of age, male homozygotes show a significantly higher frequency of abnormal cauda sperm morphology than wild-type males (~32% vs ~7%, respectively)

adipose tissue phenotype

decreased abdominal fat pad weight
- female homozygotes exhibit reduced abdominal fat deposits relative to wild-type females

endocrine/exocrine gland phenotype

abnormal adenohypophysis morphology
- the mutant anterior pituitary displays vacuolated cells, suggestiing low rates of feedback control and increased hormone synthesis and secretion

abnormal granulosa cell morphology
- at 7-8 weeks of age, mutant mural granulosa cells exhibit lipid accumulation, as shown by oil-red-O staining

abnormal ovarian follicle morphology
- at 7 weeks of age, mutant ovarian follicles and stromata exhibit lipid accumulation, as shown by oil-red-O staining

abnormal ovarian secretion
- adult mutant ovaries show near absence of 17beta-estradiol (E2) content (2.0 pg) relative to 110-135 pg/ovary in wild-type controls
- expression of two key steroidogenic proteins (StAR and Cyp19) is markedly reduced in mutant ovaries relative to wild-type controls
- however, exogenous gonadotropin treatment restores expression of both steroidogenic proteins to wild-type levels

abnormal ovary morphology
- at 7-8 weeks of age, the stromata of mutant ovaries contain numerous islands of foamy cells composed of healthy nuclei and vacuolated cytoplasm
- these cell nests are replete with lipid, as shown by oil-red-O staining

abnormal secondary ovarian follicle morphology
- at 7 weeks of age, mutant antral follicles are smaller than the largest follicles found in wild-type controls
- chronic treatment of 8-wk-old female mutants with 17beta-estradiol (E2) increases the number of secondary and large antral follicles, well in excess of that found in untreated mutant ovaries
- exogenous gonadotropin treatment induces development of numerous large antral follicles at 48 hrs in both wild-type and mutant ovaries; however, mutant ovaries display fewer large follicles in response to eCG
- the number of mutant secondary and antral follicles is reduced relative to wild-type controls

absent corpus luteum
- at 7-8 weeks of age, no formation of corpora lutea is observed
- injection of hCG after eCG treatment induces formation of corpora lutea in both wild-type and mutant mice; however, less than half the number of corpora lutea are detected in mutant ovaries

absent mature ovarian follicles
- mutant ovarian follicles fail to mature to the large antral and preovulatory stages

adenohypophysis hypoplasia
- the mutant anterior pituitary is hypoplastic relative to wild-type

decreased endometrial gland number
- at 7-8 weeks of age, reduction in the endometrial stroma is associated with a reduction in the convolution of uterine glands

decreased lactotroph cell number
- however, chronic (4-week) treatment with 17beta-estradiol (E2) restores pituitary volume and acidophil numbers to wild-type levels
- the mutant anterior pituitary shows a dramatic reduction in acidophil cell number relative to wild-type

decreased ovary weight
- at 7-8 weeks of age, the average weight of mutant ovaries is 1.1 +/- 0.22 mg vs 4.76 +/- 0.51 mg for wild-type ovaries

seminiferous tubule degeneration
- some mutant seminiferous tubules exhibit evidence of extensive degeneration

small ovary
- at 7-8 weeks, but not at 3 weeks, of age mutant ovaries are smaller than wild-type

cardiovascular system phenotype

abnormal lung vasculature morphology
- capillary endothelial cells containing enlarged vacuoles/multivesicular bodies are seen in the lungs
- enlarged polymorphonuclear leukocytes or circulating macrophages filled with vacuolar inclusions are seen within lung capillaries

behavior/neurological phenotype

abnormal motor capabilities/coordination/movement
- defects beginning at 7 to 8 weeks of age

decreased food intake
- poor food intake, beginning at 7 weeks of age

impaired coordination
- mice exhibit impaired coordination around 40 days of age with coordination worsening as the mice age

growth/size/body region phenotype

decreased body size
- female homozygotes display a smaller stature than wild-type females

decreased body weight
- female homozygotes display a reduced body mass relative to wild-type females

weight loss
- beginning at 7 to 8 weeks of age
- mice exhibit weight loss starting at 40 days of age

hematopoietic system phenotype

abnormal alveolar macrophage morphology
- alveolar macrophages are enlarged and vacuole-filled, some with concentric multilamellar electron dense surfactant-like materials
- alveolar macrophages are laden with free cholesterol with many large, foamy cells; phospholipid levels are elevated 6-fold and cholesterol levels are elevated 15-fold in alveolar macrophages

enlarged spleen
- progressive splenomegaly, beginning at 7 weeks of age

homeostasis/metabolism phenotype

abnormal cellular cholesterol metabolism
- higher rate of turnover although whole body pool is considerably elevated
- rate of cholesterol synthesis is reduced

abnormal lipid level
- elevation in lipid content in the lungs

abnormal phospholipid level
- 2- to 2.8-fold increase in phospholipid levels in lamellar bodies
- 4-fold elevation of phospholipid levels of bronchoalveolar lavage
- increase in phospholipid content in the lungs
- increase in surfactant phospholipid levels

decreased brain cholesterol level
- decreased levels in the brain at 7 weeks of age relative to controls
- mice have decreased levels of total cholesterol in the brain

decreased circulating prolactin level
- female homozygotes show a dramatic reduction in serum prolactin levels relative to wild-type controls

decreased prolactin level
- however, chronic (4-week) treatment with 17beta-estradiol (E2) dramatically increases the cytoplasmic signal for prolactin, well in excess of that found in wild-type pituitaries
- mutant pituitaries exhibit decreased concentrations of prolactin, consistent with a significant reduction in pituitary prolactin mRNA

increased cholesterol level
- 12-fold elevation of cholesterol levels in branchoalveolar lavage
- 6.8-fold increase in cholesterol levels in lamellar bodies
- elevated in most organs except the brain at 7 weeks of age
- elevated in the brain at 1 day of age
- increase in cholesterol content in the lungs
- mice have increased cholesterol levels in the liver, spleen, intestine and lung

increased circulating cholesterol level
- progressively increasing plasma cholesterol levels

increased circulating follicle stimulating hormone level
- female homozygotes show a 25% increase in serum FSH levels relative to wild-type controls

increased circulating luteinizing hormone level
- female homozygotes show a dramatic increase in serum LH levels relative to wild-type controls
- in contrast, pituitary expression and circulating levels of GH remain unaffected

lipidosis
- at 7-8 weeks of age, female homozygotes show lipid accumulation in mural granulosa cells and in the ovarian stroma, as shown by oil-red-O staining
- lipid accumulation (including sphingomyelin, glucocerebroside, lactosylceramide, and cholesterol) in various organs including the liver, lung, kidney, thymus, spleen, and brain
- lungs exhibit surfactant accumulation, indicating alveolar lipidosis

pulmonary alveolar proteinosis
- mild protein accumulation in bronchoalveolar lavage
- proteinaceous-like material in the alveolar space

immune system phenotype

abnormal alveolar macrophage morphology
- alveolar macrophages are enlarged and vacuole-filled, some with concentric multilamellar electron dense surfactant-like materials
- alveolar macrophages are laden with free cholesterol with many large, foamy cells; phospholipid levels are elevated 6-fold and cholesterol levels are elevated 15-fold in alveolar macrophages

enlarged spleen
- progressive splenomegaly, beginning at 7 weeks of age

liver/biliary system phenotype

enlarged liver
- hepatomegaly and associated pale liver, presumably due to lipid accumulation

hepatic steatosis
- massive liver storage of cholesterol in mice on a high fat, 1% cholesterol diet

increased liver weight
- progressive increase in liver weight, beginning at 7 weeks of age

pale liver

reproductive system phenotype

abnormal female reproductive system morphology
- at 7-8 weeks of age, female homozygotes exhibit a thinner reproductive tract than wild-type females

abnormal granulosa cell morphology
- at 7-8 weeks of age, mutant mural granulosa cells exhibit lipid accumulation, as shown by oil-red-O staining

abnormal ovarian follicle morphology
- at 7 weeks of age, mutant ovarian follicles and stromata exhibit lipid accumulation, as shown by oil-red-O staining

abnormal ovarian secretion
- adult mutant ovaries show near absence of 17beta-estradiol (E2) content (2.0 pg) relative to 110-135 pg/ovary in wild-type controls
- expression of two key steroidogenic proteins (StAR and Cyp19) is markedly reduced in mutant ovaries relative to wild-type controls
- however, exogenous gonadotropin treatment restores expression of both steroidogenic proteins to wild-type levels

abnormal ovary morphology
- at 7-8 weeks of age, the stromata of mutant ovaries contain numerous islands of foamy cells composed of healthy nuclei and vacuolated cytoplasm
- these cell nests are replete with lipid, as shown by oil-red-O staining

abnormal secondary ovarian follicle morphology
- at 7 weeks of age, mutant antral follicles are smaller than the largest follicles found in wild-type controls
- chronic treatment of 8-wk-old female mutants with 17beta-estradiol (E2) increases the number of secondary and large antral follicles, well in excess of that found in untreated mutant ovaries
- exogenous gonadotropin treatment induces development of numerous large antral follicles at 48 hrs in both wild-type and mutant ovaries; however, mutant ovaries display fewer large follicles in response to eCG
- the number of mutant secondary and antral follicles is reduced relative to wild-type controls

abnormal sperm head morphology
- at 60 days of age, aberrant cauda sperm heads are frequentyly observed

absent corpus luteum
- at 7-8 weeks of age, no formation of corpora lutea is observed
- injection of hCG after eCG treatment induces formation of corpora lutea in both wild-type and mutant mice; however, less than half the number of corpora lutea are detected in mutant ovaries

absent estrous cycle
- female homozygotes are acyclic

absent mature ovarian follicles
- mutant ovarian follicles fail to mature to the large antral and preovulatory stages

absent sperm flagellum
- at 60 days of age, tailless sperm heads are frequently observed

absent sperm head
- at 60 days of age, headless sperm tails are frequently observed

anovulation
- at 7-8 weeks of age, mutant ovaries display no evidence of ovulation
- exogenous gonadotropin treatment induces ovulation in both wild-type and mutant ovaries; however, mutant ovaries exhibit fewer large follicles in response to eCG and fewer ovulations in response hCG
- mutant ovaries transplanted under wild-type kidney capsules display evidence of ovulation, as shown by the presence of corpora lutea and an extraovarian oocyte

arrest of spermatogenesis
- male homozygotes show a partial arrest of spermatogenesis, with some tubules containing fused spermatogenic cells with more than one nucleus while other tubules appear normal

decreased endometrial gland number
- at 7-8 weeks of age, reduction in the endometrial stroma is associated with a reduction in the convolution of uterine glands

decreased ovary weight
- at 7-8 weeks of age, the average weight of mutant ovaries is 1.1 +/- 0.22 mg vs 4.76 +/- 0.51 mg for wild-type ovaries

endometrium atrophy

female infertility
- female homozygotes are infertile

impaired acrosome reaction
- in vitro, mutant sperm are able to bind to zona-free eggs as well as wild-type sperm but fail to fuse with the egg plasma membrane
- interestingly, 30% of total cyritestin protein is not proteolytically processed on mutant cauda sperm, whereas fertilin beta is processed normally
- when zona-intact eggs are used, the in vitro capacity of mutant sperm to bind to the egg zona pellucida is only 14% of the level in wild-type sperm

impaired fertilization
- in vitro, mutant sperm are unable to fertilize cumulus-intact eggs (CIE) and produce two-cell embryos, unlike wild-type sperm which fertilize ~56% of CIE

infertility
- females showed normal oogenesis, but lacked implantation sites after successful plugging

male infertility
- male homozygotes are infertile

oligozoospermia
- at 60 days of age, the total number of mutant cauda sperm is reduced to only ~28% of that in wild-type males

seminiferous tubule degeneration
- some mutant seminiferous tubules exhibit evidence of extensive degeneration

small ovary
- at 7-8 weeks, but not at 3 weeks, of age mutant ovaries are smaller than wild-type

teratozoospermia
- at 60 days of age, male homozygotes show a significantly higher frequency of abnormal cauda sperm morphology than wild-type males (~32% vs ~7%, respectively)

thin endometrium
- at 8 weeks of age, a reduction in endometrial thickness is observed

thin myometrium

thin uterus
- at 7-8 weeks of age, mutant uteri are thinner than wild-type

uterus atrophy
- at 7-8 weeks of age, atrophy of the myometrium, endometrial stroma, and the endometrial epithelium is observed

respiratory system phenotype

abnormal alveolar lamellar body morphology
- cholesterol and phospholipid accumulation in lamellar bodies of alveolar type II cells

abnormal alveolar macrophage morphology
- alveolar macrophages are enlarged and vacuole-filled, some with concentric multilamellar electron dense surfactant-like materials
- alveolar macrophages are laden with free cholesterol with many large, foamy cells; phospholipid levels are elevated 6-fold and cholesterol levels are elevated 15-fold in alveolar macrophages

abnormal lung morphology
- lungs contain 'nests' of vacuolar filled macrophages and enlarged foamy alveolar macrophages

abnormal lung vasculature morphology
- capillary endothelial cells containing enlarged vacuoles/multivesicular bodies are seen in the lungs
- enlarged polymorphonuclear leukocytes or circulating macrophages filled with vacuolar inclusions are seen within lung capillaries

abnormal respiratory system physiology
- liposome degradation is reduced by 46% in the lungs

abnormal surfactant composition
- increase in surfactant phospholipid levels

abnormal type II pneumocyte morphology
- alveolar type II cells have many autophagosomes

enlarged alveolar lamellar bodies
- 42% of alveolar type II cell lamellar bodies are enlarged compared to 15% in wild-type mice

increased lung weight
- lung weight as a % of total body weight is higher
- progressive increase in lung weight, beginning at 7 weeks of age

pulmonary alveolar proteinosis
- mild protein accumulation in bronchoalveolar lavage
- proteinaceous-like material in the alveolar space

thick pulmonary interalveolar septum
- thickening of the intra-alveolar septae with a slight enlargement of the airways

The following phenotype information is associated with a similar, but not exact match to this JAX^® Mice strain

Genotype: Npc1^m1N/Npc1^m1N
B6.C-Npc1^m1N

nervous system phenotype

Purkinje cell degeneration
- at 7 weeks

astrocytosis

microgliosis

hematopoietic system phenotype

microgliosis

homeostasis/metabolism phenotype

abnormal ceramide level
- Background Sensitivity - increased accumulation in P49 liver and brain tissue as compared to BALB/c background

abnormal lipid homeostasis

abnormal lipid level
- Background Sensitivity - increased lipid accumulation in P49 liver tissue as compared to BALB/c background
- Background Sensitivity - lipids include: ceramides, monohexosyceramides, sphingomyelins, sphingoid bases, gangiosides, free cholesterol, 24(S)-hydroxycholesterol, 4beta-hydroxy cholesterol and cholesterol ester

abnormal sphingomyelin level
- Background Sensitivity - increased accumulation in P49 liver tissue as compared to BALB/c background

increased cholesterol level
- mice exhibit an increase in unestrified cholesterol in the cerebellum compared with wild-type mice

increased liver cholesterol level
- Background Sensitivity - increased accumulation in P49 liver tissue as compared to BALB/c background

cellular phenotype

foam cell reticulosis
- mice exhibit proliferation of foamy cells in the liver unlike wild-type mice

immune system phenotype

microgliosis

liver/biliary system phenotype

increased liver cholesterol level
- Background Sensitivity - increased accumulation in P49 liver tissue as compared to BALB/c background

Genotype: Npc1^m1N/Npc1^m1N
involves: 129S1/Sv * BALB/c * C57BL/6

mortality/aging

premature death
- all mice on a genetic background involving 129S1/Sv, C57BL/6, and BALB/c died by ~120 days of age

growth/size/body region phenotype

weight loss
- earlier onset and faster progression than in Npc2^tm1Plob homozygotes

homeostasis/metabolism phenotype

abnormal lipid homeostasis
- cholesterol and other lipid accumulation in the liver at 50 days of age with an ~17 fold increase in plant sterols and marked elevations of sphingomyelin, lyso(bis)phosphatidic acid, gangliosides GM2 and GM3, glucosylceramide, lactosylceramide, and asialo-GM2-GM2
- galactosylceramide levels were reduced in the brain, reflecting a general loss of myelin lipids
- lipid accumulation in the brain at 50 days was largely limited to glycolipids with 11 to 15 fold increases in glucosylceramide, lactosylceramide, and asialo-GM2

increased liver cholesterol level
- about a 10 fold increase in total cholesterol accumulation in the liver at 50 days of age
- about a 6 fold increase in total cholesterol accumulation in the liver at 28 days of age
- no increase in overall cholesterol levels in the brain, putatively due to compensatory losses due to demyelination, neuronal death, and possible imbalance between neuronal cell bodies and distal axons
- on the cellular level in the brain, unesterified cholesterol was stored in neurons within the neocortex, dentate gyrus, hippocampus, and cerebellum

nervous system phenotype

Purkinje cell degeneration

liver/biliary system phenotype

increased liver cholesterol level
- about a 10 fold increase in total cholesterol accumulation in the liver at 50 days of age
- about a 6 fold increase in total cholesterol accumulation in the liver at 28 days of age
- no increase in overall cholesterol levels in the brain, putatively due to compensatory losses due to demyelination, neuronal death, and possible imbalance between neuronal cell bodies and distal axons
- on the cellular level in the brain, unesterified cholesterol was stored in neurons within the neocortex, dentate gyrus, hippocampus, and cerebellum

Genotype: Npc1^m1N/Npc1^m1N
involves: 129S2/SvPas * BALB/c * C57BL/6

mortality/aging

premature death
- lifespan of Npc1-null mice expressing Il6 is modestly reduced compared to double null littermates

Genotype: Npc1^m1N/Npc1^m1N
involves: BALB/c * C3H/HeJ * C57BL/6J

mortality/aging

premature death
- mutants exhibit a reduced lifespan with only 30% of mice living past 90 days
- mutants treated with 2-hydroxypropyl-beta-cyclodextrin (2-HPC) at P7 to lower cholesterol accumulation live significantly longer than saline-injected mutants, with a median survival of 107 days versus 85 days

behavior/neurological phenotype

abnormal object recognition memory
- mutants exhibit deficits in object memory index at 10 weeks of age, but not at 7 weeks of age, on the object recognition memory test
- mutants treated with 2-HPC at P7 to lower cholesterol accumulation show significant improvement in cognitive performance

hypoactivity
- mutants exhibit reduced locomotor activity and increased periods of inactivity in open-field tests at 10 weeks of age
- mutants treated with 2-HPC at P7 to lower cholesterol accumulation show significant improvement in motor performance

impaired coordination
- mutants exhibit impaired rotarod performance and gait coordination at 10 weeks of age but not at 4 or 7 weeks of age
- mutants treated with 2-HPC at P7 to lower cholesterol accumulation show significant improvement in motor performance

nervous system phenotype

Purkinje cell degeneration
- decrease in the number of cerebellar Purkinje cells; cell loss is less pronounced than in double Npc1 and Tg(PRNP-APPSweInd)8Dwst mutants
- however neuronal loss in the hippocampus is not seen
- mutants treated with 2-HPC at P7 to lower cholesterol accumulation show decreased Purkinje cell loss compared to saline-injected mutants

demyelination
- mutants exhibit demyelination in the hippocampus/cortex and cerebellum, however demyelination is less severe than in double Npc1 and Tg(PRNP-APPSweInd)8Dwst mutants at earlier stages

increased brain cholesterol level
- however total cholesterol content in the hippocampus and cerebellum is not altered compared with controls
- mutants exhibit intracellular accumulation of unesterified cholesterol in the hippocampus and cerebellum at 4, 7, and 10 weeks of age

microgliosis
- mutants exhibit microglial activation in the hippocampus and cerebellum, however at a lower level than in double Npc1 and Tg(PRNP-APPSweInd)8Dwst mutants
- mutants treated with 2-HPC at P7 to lower cholesterol accumulation show lower microglia activation compared to saline-injected mutants

neurodegeneration
- neurodgeneration in the cerebellum

hematopoietic system phenotype

microgliosis
- mutants exhibit microglial activation in the hippocampus and cerebellum, however at a lower level than in double Npc1 and Tg(PRNP-APPSweInd)8Dwst mutants
- mutants treated with 2-HPC at P7 to lower cholesterol accumulation show lower microglia activation compared to saline-injected mutants

homeostasis/metabolism phenotype

abnormal enzyme/coenzyme level
- cathepsin D levels and activity are higher in the hippocampus and the cerebellum than in controls, although this is lower than in double Npc1 and Tg(PRNP-APPSweInd)8Dwst mutants
- cytosolic cathepsin D, cytochrome c and Bcl-2-associated X protein levels are increased in the cerebellum although to a lower level than in double Npc1 and Tg(PRNP-APPSweInd)8Dwst mutants

increased brain cholesterol level
- however total cholesterol content in the hippocampus and cerebellum is not altered compared with controls
- mutants exhibit intracellular accumulation of unesterified cholesterol in the hippocampus and cerebellum at 4, 7, and 10 weeks of age

immune system phenotype

microgliosis
- mutants exhibit microglial activation in the hippocampus and cerebellum, however at a lower level than in double Npc1 and Tg(PRNP-APPSweInd)8Dwst mutants
- mutants treated with 2-HPC at P7 to lower cholesterol accumulation show lower microglia activation compared to saline-injected mutants

References

Additional References

Baudry M; Yao Y; Simmons D; Liu J; Bi X. 2003. Postnatal development of inflammation in a murine model of Niemann-Pick type C disease: immunohistochemical observations of microglia and astroglia. Exp Neurol 184(2):887-903. PubMed: 14769381 MGI: J:87264
Burns M; Gaynor K; Olm V; Mercken M; LaFrancois J; Wang L; Mathews PM; Noble W; Matsuoka Y; Duff K. 2003. Presenilin redistribution associated with aberrant cholesterol transport enhances beta-amyloid production in vivo. J Neurosci 23(13):5645-9. PubMed: 12843267 MGI: J:84370
Karten B; Vance DE; Campenot RB; Vance JE. 2002. Cholesterol accumulates in cell bodies, but is decreased in distal axons, of Niemann-Pick C1-deficient neurons. J Neurochem 83(5):1154-63. PubMed: 12437586 MGI: J:80447
Miyawaki S; Mitsuoka S; Sakiyama T; Kitagawa T. 1983. Time course of hepatic lipids accumulation in a strain of mice with an inherited deficiency of sphingomyelinase. J Hered 74(6):465-8. PubMed: 6315811 MGI: J:7245
Miyawaki S; Mitsuoka S; Sakiyama T; Kitagawa T. 1982. Sphingomyelinosis, a new mutation in the mouse: a model of Niemann-Pick disease in humans. J Hered 73(4):257-63. PubMed: 7202025 MGI: J:6833
Miyawaki S; Yoshida H; Mitsuoka S; Enomoto H; Ikehara S. 1986. A mouse model for Niemann-Pick disease. Influence of genetic background on disease expression in spm/spm mice. J Hered 77(6):379-84. PubMed: 3559164 MGI: J:8630
Morris MD; Bhuvaneswaran C; Shio H; Fowler S. 1982. Lysosome lipid storage disorder in NCTR-BALB/c mice. I. Description of the disease and genetics. Am J Pathol 108(2):140-9. PubMed: 6765731 MGI: J:10212
Pentchev PG; Gal AE; Booth AD; Omodeo-Sale F; Fouks J; Neumeyer BA; Quirk JM; Dawson G; Brady RO. 1980. A lysosomal storage disorder in mice characterized by a dual deficiency of sphingomyelinase and glucocerebrosidase. Biochim Biophys Acta 619(3):669-79. PubMed: 6257302 MGI: J:18511

Additional - Npc1^m1N related

Abi-Mosleh L; Infante RE; Radhakrishnan A; Goldstein JL; Brown MS. 2009. Cyclodextrin overcomes deficient lysosome-to-endoplasmic reticulum transport of cholesterol in Niemann-Pick type C cells. Proc Natl Acad Sci U S A 106(46):19316-21. PubMed: 19884502 MGI: J:154766
Akpovi CD; Murphy BD; Erickson RP; Pelletier RM. 2014. Dysregulation of testicular cholesterol metabolism following spontaneous mutation of the niemann-pick c1 gene in mice. Biol Reprod 91(2):42. PubMed: 25009206 MGI: J:213845
Alam MS; Getz M; Safeukui I; Yi S; Tamez P; Shin J; Velazquez P; Haldar K. 2012. Genomic expression analyses reveal lysosomal, innate immunity proteins, as disease correlates in murine models of a lysosomal storage disorder. PLoS One 7(10):e48273. PubMed: 23094108 MGI: J:192177
Alam MS; Getz M; Yi S; Kurkewich J; Safeukui I; Haldar K. 2014. Plasma signature of neurological disease in the monogenetic disorder Niemann-Pick Type C. J Biol Chem 289(12):8051-66. PubMed: 24488491 MGI: J:211208
Alvarez AR; Klein A; Castro J; Cancino GI; Amigo J; Mosqueira M; Vargas LM; Yevenes LF; Bronfman FC; Zanlungo S. 2008. Imatinib therapy blocks cerebellar apoptosis and improves neurological symptoms in a mouse model of Niemann-Pick type C disease. FASEB J 22(10):3617-27. PubMed: 18591368 MGI: J:140248
Amigo L; Mendoza H; Castro J; Quinones V; Miquel JF; Zanlungo S. 2002. Relevance of Niemann-Pick type C1 protein expression in controlling plasma cholesterol and biliary lipid secretion in mice. Hepatology 36(4 Pt 1):819-28. PubMed: 12297829 MGI: J:106027
Amritraj A; Peake K; Kodam A; Salio C; Merighi A; Vance JE; Kar S. 2009. Increased activity and altered subcellular distribution of lysosomal enzymes determine neuronal vulnerability in Niemann-Pick type C1-deficient mice. Am J Pathol 175(6):2540-56. PubMed: 19893049 MGI: J:155318
Aqul A; Liu B; Ramirez CM; Pieper AA; Estill SJ; Burns DK; Liu B; Repa JJ; Turley SD; Dietschy JM. 2011. Unesterified cholesterol accumulation in late endosomes/lysosomes causes neurodegeneration and is prevented by driving cholesterol export from this compartment. J Neurosci 31(25):9404-13. PubMed: 21697390 MGI: J:173597
Avchalumov Y; Kirschstein T; Lukas J; Luo J; Wree A; Rolfs A; Kohling R. 2012. Increased excitability and compromised long-term potentiation in the neocortex of NPC1(-/-) mice. Brain Res 1444:20-6. PubMed: 22325094 MGI: J:181851
Baudry M; Yao Y; Simmons D; Liu J; Bi X. 2003. Postnatal development of inflammation in a murine model of Niemann-Pick type C disease: immunohistochemical observations of microglia and astroglia. Exp Neurol 184(2):887-903. PubMed: 14769381 MGI: J:87264
Beltroy EP; Liu B; Dietschy JM; Turley SD. 2007. Lysosomal unesterified cholesterol content correlates with liver cell death in murine Niemann-Pick type C disease. J Lipid Res 48(4):869-81. PubMed: 17220530 MGI: J:121676
Bhuvaneswaran C; Morris MD; Shio H; Fowler S. 1982. Lysosome lipid storage disorder in NCTR-BALB/c mice. III. Isolation and analysis of storage inclusions from liver. Am J Pathol 108(2):160-70. PubMed: 6101077 MGI: J:10214
Bi X; Liu J; Yao Y; Baudry M; Lynch G. 2005. Deregulation of the phosphatidylinositol-3 kinase signaling cascade is associated with neurodegeneration in Npc1-/- mouse brain. Am J Pathol 167(4):1081-92. PubMed: 16192643 MGI: J:101694
Boland B; Smith DA; Mooney D; Jung SS; Walsh DM; Platt FM. 2010. Macroautophagy is not directly involved in the metabolism of amyloid precursor protein. J Biol Chem 285(48):37415-26. PubMed: 20864542 MGI: J:167334
Boothe AD; Bhuvaneswaran C; Morris MD; Barry JE. 1977. Tissue cholesterol storage disorder in BALB/c mice: histologic findings Fed Proc 36:1158 (Abstr.). MGI: J:83825
Bosch B; Berger AC; Khandelwal S; Heipertz EL; Scharf B; Santambrogio L; Roche PA. 2013. Disruption of multivesicular body vesicles does not affect major histocompatibility complex (MHC) class II-peptide complex formation and antigen presentation by dendritic cells. J Biol Chem 288(34):24286-92. PubMed: 23846690 MGI: J:203447
Bu B; Li J; Davies P; Vincent I. 2002. Deregulation of cdk5, hyperphosphorylation, and cytoskeletal pathology in the Niemann-Pick type C murine model. J Neurosci 22(15):6515-25. PubMed: 12151531 MGI: J:78091
Buard I; Pfrieger FW. 2014. Relevance of neuronal and glial NPC1 for synaptic input to cerebellar Purkinje cells. Mol Cell Neurosci 61:65-71. PubMed: 24910948 MGI: J:213994
Burns M; Gaynor K; Olm V; Mercken M; LaFrancois J; Wang L; Mathews PM; Noble W; Matsuoka Y; Duff K. 2003. Presenilin redistribution associated with aberrant cholesterol transport enhances beta-amyloid production in vivo. J Neurosci 23(13):5645-9. PubMed: 12843267 MGI: J:84370
Carette JE; Raaben M; Wong AC; Herbert AS; Obernosterer G; Mulherkar N; Kuehne AI; Kranzusch PJ; Griffin AM; Ruthel G; Dal Cin P; Dye JM; Whelan SP; Chandran K; Brummelkamp TR. 2011. Ebola virus entry requires the cholesterol transporter Niemann-Pick C1. Nature 477(7364):340-3. PubMed: 21866103 MGI: J:176235
Chandler RJ; Williams IM; Gibson AL; Davidson CD; Incao AA; Hubbard BT; Porter FD; Pavan WJ; Venditti CP. 2017. Systemic AAV9 gene therapy improves the lifespan of mice with Niemann-Pick disease, type C1. Hum Mol Genet 26(1):52-64. PubMed: 27798114 MGI: J:241449
Chen G; Li HM; Chen YR; Gu XS; Duan S. 2007. Decreased estradiol release from astrocytes contributes to the neurodegeneration in a mouse model of Niemann-Pick disease type C. Glia 55(15):1509-18. PubMed: 17705200 MGI: J:156298
Chung C; Elrick MJ; Dell'Orco JM; Qin ZS; Kalyana-Sundaram S; Chinnaiyan AM; Shakkottai VG; Lieberman AP. 2016. Heat Shock Protein Beta-1 Modifies Anterior to Posterior Purkinje Cell Vulnerability in a Mouse Model of Niemann-Pick Type C Disease. PLoS Genet 12(5):e1006042. PubMed: 27152617 MGI: J:232553
Claudepierre T; Paques M; Simonutti M; Buard I; Sahel J; Maue RA; Picaud S; Pfrieger FW. 2010. Lack of Niemann-Pick type C1 induces age-related degeneration in the mouse retina. Mol Cell Neurosci 43(1):164-76. PubMed: 19883762 MGI: J:158305
D'Arcangelo G; Grossi D; De Chiara G; de Stefano MC; Cortese G; Citro G; Rufini S; Tancredi V; Merlo D; Frank C. 2011. Glutamatergic neurotransmission in a mouse model of Niemann-Pick Type C Disease. Brain Res 1396:11-9. PubMed: 21575932 MGI: J:172649
Deisz RA; Meske V; Treiber-Held S; Albert F; Ohm TG. 2005. Pathological cholesterol metabolism fails to modify electrophysiological properties of afflicted neurones in Niemann-Pick disease type C. Neuroscience 130(4):867-73. PubMed: 15652985 MGI: J:105214
Demais V; Barthelemy A; Perraut M; Ungerer N; Keime C; Reibel S; Pfrieger FW. 2016. Reversal of Pathologic Lipid Accumulation in NPC1-Deficient Neurons by Drug-Promoted Release of LAMP1-Coated Lamellar Inclusions. J Neurosci 36(30):8012-25. PubMed: 27466344 MGI: J:234624
Deutsch G; Muralidhar A; Le E; Borbon IA; Erickson RP. 2016. Extensive macrophage accumulation in young and old Niemann-Pick C1 model mice involves the alternative, M2, activation pathway and inhibition of macrophage apoptosis. Gene 578(2):242-50. PubMed: 26707209 MGI: J:231336
Dixit SS; Jadot M; Sohar I; Sleat DE; Stock AM; Lobel P. 2011. Loss of niemann-pick c1 or c2 protein results in similar biochemical changes suggesting that these proteins function in a common lysosomal pathway. PLoS One 6(8):e23677. PubMed: 21887293 MGI: J:176152
Dixit SS; Sleat DE; Stock AM; Lobel P. 2007. Do mammalian NPC1 and NPC2 play a role in intestinal cholesterol absorption? Biochem J 408(1):1-5. PubMed: 17880278 MGI: J:126287
Elrick MJ; Pacheco CD; Yu T; Dadgar N; Shakkottai VG; Ware C; Paulson HL; Lieberman AP. 2010. Conditional Niemann-Pick C mice demonstrate cell autonomous Purkinje cell neurodegeneration. Hum Mol Genet 19(5):837-47. PubMed: 20007718 MGI: J:157113
Elrick MJ; Yu T; Chung C; Lieberman AP. 2012. Impaired proteolysis underlies autophagic dysfunction in Niemann-Pick type C disease. Hum Mol Genet 21(22):4876-87. PubMed: 22872701 MGI: J:188344
Erickson RP; Bhattacharyya A; Hunter RJ; Heidenreich RA; Cherrington NJ. 2005. Liver disease with altered bile acid transport in Niemann-Pick C mice on a high-fat, 1% cholesterol diet. Am J Physiol Gastrointest Liver Physiol 289(2):G300-7. PubMed: 15790756 MGI: J:100351
Erickson RP; Garver WS; Camargo F; Hossain GS; Heidenreich RA. 2000. Pharmacological and genetic modifications of somatic cholesterol do not substantially alter the course of CNS disease in Niemann-Pick C mice J Inherit Metab Dis 23(1):54-62. PubMed: 10682308 MGI: J:60459
Erickson RP; Kiela M; Devine PJ; Hoyer PB; Heidenreich RA. 2002. mdr1a deficiency corrects sterility in Niemann-Pick C1 protein deficient female mice. Mol Reprod Dev 62(2):167-73. PubMed: 11984826 MGI: J:76395
Erickson RP; Kiela M; Garver WS; Krishnan K; Heidenreich RA. 2001. Cholesterol signaling at the endoplasmic reticulum occurs in npc1(-/-) but not in npc1(-/-), LDLR(-/-) mice. Biochem Biophys Res Commun 284(2):326-30. PubMed: 11394880 MGI: J:69915
Fan J; Akabane H; Graham SN; Richardson LL; Zhu GZ. 2006. Sperm defects in mice lacking a functional Niemann-Pick C1 protein. Mol Reprod Dev 73(10):1284-91. PubMed: 16850391 MGI: J:119302
Fan M; Sidhu R; Fujiwara H; Tortelli B; Zhang J; Davidson C; Walkley SU; Bagel JH; Vite C; Yanjanin NM; Porter FD; Schaffer JE; Ory DS. 2013. Identification of Niemann-Pick C1 disease biomarkers through sphingolipid profiling. J Lipid Res 54(10):2800-14. PubMed: 23881911 MGI: J:202626
Fu R; Wassif CA; Yanjanin NM; Watkins-Chow DE; Baxter LL; Incao A; Liscum L; Sidhu R; Firnkes S; Graham M; Ory DS; Porter FD; Pavan WJ. 2013. Efficacy of N-acetylcysteine in phenotypic suppression of mouse models of Niemann-Pick disease, type C1. Hum Mol Genet 22(17):3508-23. PubMed: 23666527 MGI: J:199190
Gadola SD; Silk JD; Jeans A; Illarionov PA; Salio M; Besra GS; Dwek R; Butters TD; Platt FM; Cerundolo V. 2006. Impaired selection of invariant natural killer T cells in diverse mouse models of glycosphingolipid lysosomal storage diseases. J Exp Med 203(10):2293-303. PubMed: 16982810 MGI: J:124639
German DC; Liang CL; Song T; Yazdani U; Xie C; Dietschy JM. 2002. Neurodegeneration in the Niemann-Pick C mouse: glial involvement. Neuroscience 109(3):437-50. PubMed: 11823057 MGI: J:126856
German DC; Quintero EM; Liang C; Xie C; Dietschy JM. 2001. Degeneration of neurons and glia in the Niemann-Pick C mouse is unrelated to the low-density lipoprotein receptor. Neuroscience 105(4):999-1005. PubMed: 11530237 MGI: J:126474
Gevry NY; Lopes FL; Ledoux S; Murphy BD. 2004. Aberrant intracellular cholesterol transport disrupts pituitary and ovarian function. Mol Endocrinol 18(7):1778-86. PubMed: 15105438 MGI: J:91430
Gevry NY; Murphy BD. 2002. The role and regulation of the Niemann-Pick C1 gene in adrenal steroidogenesis. Endocr Res 28(4):403-12. PubMed: 12530642 MGI: J:91497
Gondre-Lewis MC; McGlynn R; Walkley SU. 2003. Cholesterol accumulation in NPC1-deficient neurons is ganglioside dependent. Curr Biol 13(15):1324-9. PubMed: 12906793 MGI: J:95799
Goodrum JF; Pentchev PG. 1997. Cholesterol reutilization during myelination of regenerating PNS axons is impaired in Niemann-Pick disease type C mice. J Neurosci Res 49(3):389-92. PubMed: 9260750 MGI: J:42120
Griffin LD; Gong W; Verot L; Mellon SH. 2004. Niemann-Pick type C disease involves disrupted neurosteroidogenesis and responds to allopregnanolone. Nat Med 10(7):704-11. PubMed: 15208706 MGI: J:91682
Hallows JL; Iosif RE; Biasell RD; Vincent I. 2006. p35/p25 is not essential for tau and cytoskeletal pathology or neuronal loss in Niemann-Pick type C disease. J Neurosci 26(10):2738-44. PubMed: 16525053 MGI: J:106228
Hawes CM; Wiemer H; Krueger SR; Karten B. 2010. Pre-synaptic defects of NPC1-deficient hippocampal neurons are not directly related to plasma membrane cholesterol. J Neurochem 114(1):311-22. PubMed: 20456004 MGI: J:161819
Henderson LP; Lin L; Prasad A; Paul CA; Chang TY; Maue RA. 2000. Embryonic striatal neurons from niemann-pick type C mice exhibit defects in cholesterol metabolism and neurotrophin responsiveness. J Biol Chem 275(26):20179-87. PubMed: 10770933 MGI: J:110802
Higashi Y; Murayama S; Pentchev PG; Suzuki K. 1995. Peripheral nerve pathology in Niemann-Pick type C mouse. Acta Neuropathol (Berl) 90(2):158-63. PubMed: 7484091 MGI: J:28629
Higashi Y; Murayama S; Pentchev PG; Suzuki K. 1993. Cerebellar degeneration in the Niemann-Pick type C mouse. Acta Neuropathol (Berl) 85(2):175-84. PubMed: 8382896 MGI: J:4992
Holtta-Vuori M; Vainio S; Kauppi M; Van Eck M; Jokitalo E; Ikonen E. 2012. Endosomal actin remodeling by coronin-1A controls lipoprotein uptake and degradation in macrophages. Circ Res 110(3):450-5. PubMed: 22223354 MGI: J:192698
Hovakimyan M; Maass F; Petersen J; Holzmann C; Witt M; Lukas J; Frech MJ; Hubner R; Rolfs A; Wree A. 2013. Combined therapy with cyclodextrin/allopregnanolone and miglustat improves motor but not cognitive functions in Niemann-Pick Type C1 mice. Neuroscience 252:201-11. PubMed: 23948640 MGI: J:207440
Hovakimyan M; Meyer A; Lukas J; Luo J; Gudziol V; Hummel T; Rolfs A; Wree A; Witt M. 2013. Olfactory deficits in Niemann-Pick type C1 (NPC1) disease. PLoS One 8(12):e82216. PubMed: 24391715 MGI: J:209834
Hovakimyan M; Petersen J; Maass F; Reichard M; Witt M; Lukas J; Stachs O; Guthoff R; Rolfs A; Wree A. 2011. Corneal alterations during combined therapy with cyclodextrin/allopregnanolone and miglustat in a knock-out mouse model of NPC1 disease. PLoS One 6(12):e28418. PubMed: 22163015 MGI: J:182268
Ishibashi M; Masson D; Westerterp M; Wang N; Sayers S; Li R; Welch CL; Tall AR. 2010. Reduced VLDL clearance in Apoe(-/-)Npc1(-/-) mice is associated with increased Pcsk9 and Idol expression and decreased hepatic LDL-receptor levels. J Lipid Res 51(9):2655-63. PubMed: 20562239 MGI: J:164461
Jelinek D; Castillo JJ; Garver WS. 2013. The C57BL/6J Niemann-Pick C1 mouse model with decreased gene dosage has impaired glucose tolerance independent of body weight. Gene 527(1):65-70. PubMed: 23769925 MGI: J:200780
Jelinek D; Castillo JJ; Heidenreich RA; Garver WS. 2015. The C57BL/6J Niemann-Pick C1 mouse model with decreased gene dosage is susceptible to increased weight gain when fed a high-fat diet: Confirmation of a gene-diet interaction. Gene 568(1):112-3. PubMed: 25979674 MGI: J:224934
Jelinek D; Millward V; Birdi A; Trouard TP; Heidenreich RA; Garver WS. 2011. Npc1 haploinsufficiency promotes weight gain and metabolic features associated with insulin resistance. Hum Mol Genet 20(2):312-21. PubMed: 21036943 MGI: J:166906
Jelinek DA; Maghsoodi B; Borbon IA; Hardwick RN; Cherrington NJ; Erickson RP. 2012. Genetic variation in the mouse model of Niemann Pick C1 affects female, as well as male, adiposity, and hepatic bile transporters but has indeterminate effects on caveolae. Gene 491(2):128-34. PubMed: 22020183 MGI: J:179071
Kaptzan T; West SA; Holicky EL; Wheatley CL; Marks DL; Wang T; Peake KB; Vance J; Walkley SU; Pagano RE. 2009. Development of a Rab9 transgenic mouse and its ability to increase the lifespan of a murine model of Niemann-Pick type C disease. Am J Pathol 174(1):14-20. PubMed: 19056848 MGI: J:144240
Karten B; Campenot RB; Vance DE; Vance JE. 2006. The Niemann-Pick C1 protein in recycling endosomes of presynaptic nerve terminals. J Lipid Res 47(3):504-14. PubMed: 16340014 MGI: J:107557
Karten B; Hayashi H; Francis GA; Campenot RB; Vance DE; Vance JE. 2005. Generation and function of astroglial lipoproteins from Niemann-Pick type C1-deficient mice. Biochem J 387(Pt 3):779-88. PubMed: 15544574 MGI: J:117523
Karten B; Vance DE; Campenot RB; Vance JE. 2003. Trafficking of Cholesterol from Cell Bodies to Distal Axons in Niemann Pick C1-deficient Neurons. J Biol Chem 278(6):4168-75. PubMed: 12458210 MGI: J:81676
Karten B; Vance DE; Campenot RB; Vance JE. 2002. Cholesterol accumulates in cell bodies, but is decreased in distal axons, of Niemann-Pick C1-deficient neurons. J Neurochem 83(5):1154-63. PubMed: 12437586 MGI: J:80447
Kennedy BE; Hundert AS; Goguen D; Weaver IC; Karten B. 2016. Presymptomatic Alterations in Amino Acid Metabolism and DNA Methylation in the Cerebellum of a Murine Model of Niemann-Pick Type C Disease. Am J Pathol 186(6):1582-97. PubMed: 27083515 MGI: J:233698
Kennedy BE; LeBlanc VG; Mailman TM; Fice D; Burton I; Karakach TK; Karten B. 2013. Pre-symptomatic activation of antioxidant responses and alterations in glucose and pyruvate metabolism in Niemann-Pick Type C1-deficient murine brain. PLoS One 8(12):e82685. PubMed: 24367541 MGI: J:211133
Kim MJ; Kim J; Hutchinson B; Michikawa M; Cha CI; Lee B. 2005. Substance P immunoreactive cell reductions in cerebral cortex of Niemann-Pick disease type C mouse. Brain Res 1043(1-2):218-24. PubMed: 15862536 MGI: J:98024
Kim SJ; Lee BH; Lee YS; Kang KS. 2007. Defective cholesterol traffic and neuronal differentiation in neural stem cells of Niemann-Pick type C disease improved by valproic acid, a histone deacetylase inhibitor. Biochem Biophys Res Commun 360(3):593-599. PubMed: 17624314 MGI: J:123024
Klein A; Amigo L; Retamal MJ; Morales MG; Miquel JF; Rigotti A; Zanlungo S. 2006. NPC2 is expressed in human and murine liver and secreted into bile: potential implications for body cholesterol homeostasis. Hepatology 43(1):126-33. PubMed: 16374838 MGI: J:115647
Klein A; Maldonado C; Vargas LM; Gonzalez M; Robledo F; Perez de Arce K; Munoz FJ; Hetz C; Alvarez AR; Zanlungo S. 2011. Oxidative stress activates the c-Abl/p73 proapoptotic pathway in Niemann-Pick type C neurons. Neurobiol Dis 41(1):209-18. PubMed: 20883783 MGI: J:167246
Ko DC; Milenkovic L; Beier SM; Manuel H; Buchanan J; Scott MP. 2005. Cell-autonomous death of cerebellar purkinje neurons with autophagy in niemann-pick type C disease. PLoS Genet 1(1):e7. PubMed: 16103921 MGI: J:100117
Kodam A; Maulik M; Peake K; Amritraj A; Vetrivel KS; Thinakaran G; Vance JE; Kar S. 2010. Altered levels and distribution of amyloid precursor protein and its processing enzymes in Niemann-Pick type C1-deficient mouse brains. Glia 58(11):1267-81. PubMed: 20607864 MGI: J:168042
Kulinski A; Vance JE. 2007. Lipid homeostasis and lipoprotein secretion in Niemann-Pick C1-deficient hepatocytes. J Biol Chem 282(3):1627-37. PubMed: 17107950 MGI: J:118542
Langmade SJ; Gale SE; Frolov A; Mohri I; Suzuki K; Mellon SH; Walkley SU; Covey DF; Schaffer JE; Ory DS. 2006. Pregnane X receptor (PXR) activation: a mechanism for neuroprotection in a mouse model of Niemann-Pick C disease. Proc Natl Acad Sci U S A 103(37):13807-12. PubMed: 16940355 MGI: J:113746
Li H; Repa JJ; Valasek MA; Beltroy EP; Turley SD; German DC; Dietschy JM. 2005. Molecular, anatomical, and biochemical events associated with neurodegeneration in mice with Niemann-Pick type C disease. J Neuropathol Exp Neurol 64(4):323-33. PubMed: 15835268 MGI: J:104844
Li H; Turley SD; Liu B; Repa JJ; Dietschy JM. 2008. GM2/GD2 and GM3 gangliosides have no effect on cellular cholesterol pools or turnover in normal or NPC1 mice. J Lipid Res 49(8):1816-28. PubMed: 18450647 MGI: J:138451
Li X; Rydzewski N; Hider A; Zhang X; Yang J; Wang W; Gao Q; Cheng X; Xu H. 2016. A molecular mechanism to regulate lysosome motility for lysosome positioning and tubulation. Nat Cell Biol 18(4):404-17. PubMed: 26950892 MGI: J:236650
Liao G; Cheung S; Galeano J; Ji AX; Qin Q; Bi X. 2009. Allopregnanolone treatment delays cholesterol accumulation and reduces autophagic/lysosomal dysfunction and inflammation in Npc1-/- mouse brain. Brain Res 1270:140-51. PubMed: 19328188 MGI: J:156575
Liao G; Wang Z; Lee E; Moreno S; Abuelnasr O; Baudry M; Bi X. 2015. Enhanced expression of matrix metalloproteinase-12 contributes to Npc1 deficiency-induced axonal degeneration. Exp Neurol 269:67-74. PubMed: 25864931 MGI: J:225461
Liao G; Yao Y; Liu J; Yu Z; Cheung S; Xie A; Liang X; Bi X. 2007. Cholesterol accumulation is associated with lysosomal dysfunction and autophagic stress in npc1 / mouse brain. Am J Pathol 171(3):962-75. PubMed: 17631520 MGI: J:124305
Liu B; Li H; Repa JJ; Turley SD; Dietschy JM. 2008. Genetic variations and treatments that affect the lifespan of the NPC1 mouse. J Lipid Res 49(3):663-9. PubMed: 18077828 MGI: J:133425
Liu B; Ramirez CM; Miller AM; Repa JJ; Turley SD; Dietschy JM. 2010. Cyclodextrin overcomes the transport defect in nearly every organ of NPC1 mice leading to excretion of sequestered cholesterol as bile acid. J Lipid Res 51(5):933-44. PubMed: 19965601 MGI: J:160197
Liu B; Turley SD; Burns DK; Miller AM; Repa JJ; Dietschy JM. 2009. Reversal of defective lysosomal transport in NPC disease ameliorates liver dysfunction and neurodegeneration in the npc1-/- mouse. Proc Natl Acad Sci U S A 106(7):2377-82. PubMed: 19171898 MGI: J:146298
Liu B; Xie C; Richardson JA; Turley SD; Dietschy JM. 2007. Receptor-mediated and bulk-phase endocytosis cause macrophage and cholesterol accumulation in Niemann-Pick C disease. J Lipid Res 48(8):1710-23. PubMed: 17476031 MGI: J:123778
Liu Y; Wu YP; Wada R; Neufeld EB; Mullin KA; Howard AC; Pentchev PG; Vanier MT; Suzuki K; Proia RL. 2000. Alleviation of neuronal ganglioside storage does not improve the clinical course of the Niemann-Pick C disease mouse. Hum Mol Genet 9(7):1087-92. PubMed: 10767333 MGI: J:61777
Lloyd-Evans E; Morgan AJ; He X; Smith DA; Elliot-Smith E; Sillence DJ; Churchill GC; Schuchman EH; Galione A; Platt FM. 2008. Niemann-Pick disease type C1 is a sphingosine storage disease that causes deregulation of lysosomal calcium. Nat Med 14(11):1247-55. PubMed: 18953351 MGI: J:144082
Loftus SK; Erickson RP; Walkley SU; Bryant MA; Incao A; Heidenreich RA; Pavan WJ. 2002. Rescue of neurodegeneration in Niemann-Pick C mice by a prion-promoter-driven Npc1 cDNA transgene. Hum Mol Genet 11(24):3107-14. PubMed: 12417532 MGI: J:80487
Loftus SK; Morris JA; Carstea ED; Gu JZ; Cummings C; Brown A ; Ellison J ; Ohno K ; Rosenfeld MA ; Tagle DA ; Pentchev PG ; Pavan WJ. 1997. Murine model of Niemann-Pick C disease: mutation in a cholesterol homeostasis gene [see comments] Science 277(5323):232-5. PubMed: 9211850 MGI: J:41469
Lopez ME; Klein AD; Dimbil UJ; Scott MP. 2011. Anatomically defined neuron-based rescue of neurodegenerative niemann-pick type C disorder. J Neurosci 31(12):4367-78. PubMed: 21430138 MGI: J:170312
Lopez ME; Klein AD; Hong J; Dimbil UJ; Scott MP. 2012. Neuronal and epithelial cell rescue resolves chronic systemic inflammation in the lipid storage disorder Niemann-Pick C. Hum Mol Genet 21(13):2946-60. PubMed: 22493001 MGI: J:184610
Luan Z; Saito Y; Miyata H; Ohama E; Ninomiya H; Ohno K. 2008. Brainstem neuropathology in a mouse model of Niemann-Pick disease type C. J Neurol Sci 268(1-2):108-16. PubMed: 18190929 MGI: J:139928
Mari M; Caballero F; Colell A; Morales A; Caballeria J; Fernandez A; Enrich C; Fernandez-Checa JC; Garcia-Ruiz C. 2006. Mitochondrial free cholesterol loading sensitizes to TNF- and Fas-mediated steatohepatitis. Cell Metab 4(3):185-98. PubMed: 16950136 MGI: J:129725
Marques AR; Mirzaian M; Akiyama H; Wisse P; Ferraz MJ; Gaspar P; Ghauharali-van der Vlugt K; Meijer R; Giraldo P; Alfonso P; Irun P; Dahl M; Karlsson S; Pavlova EV; Cox TM; Scheij S; Verhoek M; Ottenhoff R; van Roomen CP; Pannu NS; van Eijk M; Dekker N; Boot RG; Overkleeft HS; Blommaart E; Hirabayashi Y; Aerts JM. 2016. Glucosylated cholesterol in mammalian cells and tissues: formation and degradation by multiple cellular beta-glucosidases. J Lipid Res 57(3):451-63. PubMed: 26724485 MGI: J:231478
Marschalek N; Albert F; Afshordel S; Meske V; Eckert GP; Ohm TG. 2015. Geranylgeranyl pyrophosphate is crucial for neuronal survival but has no special role in Purkinje cell degeneration in Niemann Pick type C1 disease. J Neurochem 133(1):153-61. PubMed: 25319340 MGI: J:221070
Maue RA; Burgess RW; Wang B; Wooley CM; Seburn KL; Vanier MT; Rogers MA; Chang CC; Chang TY; Harris BT; Graber DJ; Penatti CA; Porter DM; Szwergold BS; Henderson LP; Totenhagen JW; Trouard TP; Borbon IA; Erickson RP. 2012. A novel mouse model of Niemann-Pick type C disease carrying a D1005G-Npc1 mutation comparable to commonly observed human mutations. Hum Mol Genet 21(4):730-50. PubMed: 22048958 MGI: J:179744
Maulik M; Ghoshal B; Kim J; Wang Y; Yang J; Westaway D; Kar S. 2012. Mutant human APP exacerbates pathology in a mouse model of NPC and its reversal by a beta-cyclodextrin. Hum Mol Genet 21(22):4857-75. PubMed: 22869680 MGI: J:188345
Maulik M; Peake K; Chung J; Wang Y; Vance JE; Kar S. 2015. APP overexpression in the absence of NPC1 exacerbates metabolism of amyloidogenic proteins of Alzheimer's disease. Hum Mol Genet 24(24):7132-50. PubMed: 26433932 MGI: J:226837
Maulik M; Thinakaran G; Kar S. 2013. Alterations in gene expression in mutant amyloid precursor protein transgenic mice lacking Niemann-Pick type C1 protein. PLoS One 8(1):e54605. PubMed: 23382922 MGI: J:195915
Morris MD; Bhuvaneswaran C; Boothe AD. 1977. Tissue cholesterol storage disorder in BALB/c mice Fed Proc 36:1158 (Abstr.). MGI: J:83826
Morris MD; Bhuvaneswaran C; Shio H; Fowler S. 1982. Lysosome lipid storage disorder in NCTR-BALB/c mice. I. Description of the disease and genetics. Am J Pathol 108(2):140-9. PubMed: 6765731 MGI: J:10212
Muralidhar A; Borbon IA; Esharif DM; Ke W; Manacheril R; Daines M; Erickson RP. 2011. Pulmonary function and pathology in hydroxypropyl-beta-cyclodextin-treated and untreated Npc1(-/-) mice. Mol Genet Metab 103(2):142-7. PubMed: 21459030 MGI: J:172067
Nunes A; Pressey SN; Cooper JD; Soriano S. 2011. Loss of amyloid precursor protein in a mouse model of Niemann-Pick type C disease exacerbates its phenotype and disrupts tau homeostasis. Neurobiol Dis 42(3):349-59. PubMed: 21303697 MGI: J:172769
Nusca S; Canterini S; Palladino G; Bruno F; Mangia F; Erickson RP; Fiorenza MT. 2014. A marked paucity of granule cells in the developing cerebellum of the Npc1(-/-) mouse is corrected by a single injection of hydroxypropyl-beta-cyclodextrin. Neurobiol Dis 70:117-26. PubMed: 24969023 MGI: J:215476
Ohara S; Ukita Y; Ninomiya H; Ohno K. 2004. Degeneration of cholecystokinin-immunoreactive afferents to the VPL thalamus in a mouse model of Niemann-Pick disease type C. Brain Res 1022(1-2):244-6. PubMed: 15353235 MGI: J:92532
Ohara S; Ukita Y; Ninomiya H; Ohno K. 2004. Axonal dystrophy of dorsal root ganglion sensory neurons in a mouse model of Niemann-Pick disease type C. Exp Neurol 187(2):289-98. PubMed: 15144855 MGI: J:94570
Ong QR; Lim ML; Chua CC; Cheung NS; Wong BS. 2012. Impaired insulin signaling in an animal model of Niemann-Pick Type C disease. Biochem Biophys Res Commun 424(3):482-7. PubMed: 22776200 MGI: J:186234
Pacheco CD; Elrick MJ; Lieberman AP. 2009. Tau deletion exacerbates the phenotype of Niemann-Pick type C mice and implicates autophagy in pathogenesis. Hum Mol Genet 18(5):956-65. PubMed: 19074461 MGI: J:145003
Pacheco CD; Kunkel R; Lieberman AP. 2007. Autophagy in Niemann-Pick C disease is dependent upon Beclin-1 and responsive to lipid trafficking defects. Hum Mol Genet 16(12):1495-503. PubMed: 17468177 MGI: J:125097
Park S; Ahuja M; Kim MS; Brailoiu GC; Jha A; Zeng M; Baydyuk M; Wu LG; Wassif CA; Porter FD; Zerfas PM; Eckhaus MA; Brailoiu E; Shin DM; Muallem S. 2016. Fusion of lysosomes with secretory organelles leads to uncontrolled exocytosis in the lysosomal storage disease mucolipidosis type IV. EMBO Rep 17(2):266-78. PubMed: 26682800 MGI: J:237650
Parra J; Klein AD; Castro J; Morales MG; Mosqueira M; Valencia I; Cortes V; Rigotti A; Zanlungo S. 2011. Npc1 deficiency in the C57BL/6J genetic background enhances Niemann-Pick disease type C spleen pathology. Biochem Biophys Res Commun 413(3):400-6. PubMed: 21910975 MGI: J:177519
Patel SC; Suresh S; Weintroub H; Brady RO; Pentchev PG. 1987. Impaired cholesterol esterification in primary brain cultures of the lysosomal cholesterol storage disorder (LCSD) mouse mutant. Biochem Biophys Res Commun 143(1):233-40. PubMed: 3827919 MGI: J:8620
Peake KB; Campenot RB; Vance DE; Vance JE. 2011. Niemann-Pick Type C1 deficiency in microglia does not cause neuron death in vitro. Biochim Biophys Acta 1812(9):1121-9. PubMed: 21704157 MGI: J:177615
Pentchev PG; Boothe AD; Kruth HS; Weintroub H; Stivers J; Brady RO. 1984. A genetic storage disorder in BALB/C mice with a metabolic block in esterification of exogenous cholesterol. J Biol Chem 259(9):5784-91. PubMed: 6325448 MGI: J:76734
Pentchev PG; Brady RO; Blanchette-Mackie EJ; Vanier MT; Carstea ED; Parker CC; Goldin E; Roff CF. 1994. The Niemann-Pick C lesion and its relationship to the intracellular distribution and utilization of LDL cholesterol. Biochim Biophys Acta 1225(3):235-43. PubMed: 8312368 MGI: J:83835
Pentchev PG; Comly ME; Kruth HS; Patel S; Proestel M; Weintroub H. 1986. The cholesterol storage disorder of the mutant BALB/c mouse. A primary genetic lesion closely linked to defective esterification of exogenously derived cholesterol and its relationship to human type C Niemann-Pick disease. J Biol Chem 261(6):2772-7. PubMed: 3949747 MGI: J:8198
Pentchev PG; Gal AE; Booth AD; Omodeo-Sale F; Fouks J; Neumeyer BA; Quirk JM; Dawson G; Brady RO. 1980. A lysosomal storage disorder in mice characterized by a dual deficiency of sphingomyelinase and glucocerebrosidase. Biochim Biophys Acta 619(3):669-79. PubMed: 6257302 MGI: J:18511
Porter FD; Scherrer DE; Lanier MH; Langmade SJ; Molugu V; Gale SE; Olzeski D; Sidhu R; Dietzen DJ; Fu R; Wassif CA; Yanjanin NM; Marso SP; House J; Vite C; Schaffer JE; Ory DS. 2010. Cholesterol oxidation products are sensitive and specific blood-based biomarkers for Niemann-Pick C1 disease. Sci Transl Med 2(56):56ra81. PubMed: 21048217 MGI: J:168029
Praggastis M; Tortelli B; Zhang J; Fujiwara H; Sidhu R; Chacko A; Chen Z; Chung C; Lieberman AP; Sikora J; Davidson C; Walkley SU; Pipalia NH; Maxfield FR; Schaffer JE; Ory DS. 2015. A Murine Niemann-Pick C1 I1061T Knock-In Model Recapitulates the Pathological Features of the Most Prevalent Human Disease Allele. J Neurosci 35(21):8091-106. PubMed: 26019327 MGI: J:221855
Pressey SN; Smith DA; Wong AM; Platt FM; Cooper JD. 2012. Early glial activation, synaptic changes and axonal pathology in the thalamocortical system of Niemann-Pick type C1 mice. Neurobiol Dis 45(3):1086-100. PubMed: 22198570 MGI: J:182040
Qin Q; Liao G; Baudry M; Bi X. 2010. Cholesterol Perturbation in Mice Results in p53 Degradation and Axonal Pathology through p38 MAPK and Mdm2 Activation. PLoS One 5(4):e9999. PubMed: 20386595 MGI: J:160166
Quan G; Xie C; Dietschy JM; Turley SD. 2003. Ontogenesis and regulation of cholesterol metabolism in the central nervous system of the mouse. Brain Res Dev Brain Res 146(1-2):87-98. PubMed: 14643015 MGI: J:86935
Ramirez CM; Liu B; Aqul A; Taylor AM; Repa JJ; Turley SD; Dietschy JM. 2011. Quantitative role of LAL, NPC2, and NPC1 in lysosomal cholesterol processing defined by genetic and pharmacological manipulations. J Lipid Res 52(4):688-98. PubMed: 21289032 MGI: J:170933
Ramirez CM; Lopez AM; Le LQ; Posey KS; Weinberg AG; Turley SD. 2014. Ontogenic changes in lung cholesterol metabolism, lipid content, and histology in mice with Niemann-Pick type C disease. Biochim Biophys Acta 1841(1):54-61. PubMed: 24076310 MGI: J:210049
Reid PC; Sakashita N; Sugii S; Ohno-Iwashita Y; Shimada Y; Hickey WF; Chang TY. 2004. A novel cholesterol stain reveals early neuronal cholesterol accumulation in the Niemann-Pick type C1 mouse brain. J Lipid Res 45(3):582-91. PubMed: 14703504 MGI: J:88630
Reid PC; Sugii S; Chang TY. 2003. Trafficking defects in endogenously synthesized cholesterol in fibroblasts, macrophages, hepatocytes, and glial cells from Niemann-Pick type C1 mice. J Lipid Res 44(5):1010-9. PubMed: 12611909 MGI: J:83463
Repa JJ; Li H; Frank-Cannon TC; Valasek MA; Turley SD; Tansey MG; Dietschy JM. 2007. Liver X receptor activation enhances cholesterol loss from the brain, decreases neuroinflammation, and increases survival of the NPC1 mouse. J Neurosci 27(52):14470-80. PubMed: 18160655 MGI: J:130969
Richardson K; Livieratos A; Dumbill R; Hughes S; Ang G; Smith DA; Morris L; Brown LA; Peirson SN; Platt FM; Davies KE; Oliver PL. 2016. Circadian profiling in two mouse models of lysosomal storage disorders; Niemann Pick type-C and Sandhoff disease. Behav Brain Res 297:213-23. PubMed: 26467605 MGI: J:237590
Roszell BR; Tao JQ; Yu KJ; Gao L; Huang S; Ning Y; Feinstein SI; Vite CH; Bates SR. 2013. Pulmonary abnormalities in animal models due to Niemann-Pick type C1 (NPC1) or C2 (NPC2) disease. PLoS One 8(7):e67084. PubMed: 23843985 MGI: J:204311
Saez PJ; Orellana JA; Vega-Riveros N; Figueroa VA; Hernandez DE; Castro JF; Klein AD; Jiang JX; Zanlungo S; Saez JC. 2013. Disruption in connexin-based communication is associated with intracellular Ca(2)(+) signal alterations in astrocytes from Niemann-Pick type C mice. PLoS One 8(8):e71361. PubMed: 23977027 MGI: J:206348
Sagiv Y; Hudspeth K; Mattner J; Schrantz N; Stern RK; Zhou D; Savage PB; Teyton L; Bendelac A. 2006. Cutting edge: impaired glycosphingolipid trafficking and NKT cell development in mice lacking Niemann-Pick type C1 protein. J Immunol 177(1):26-30. PubMed: 16785493 MGI: J:134414
Sarkar S; Carroll B; Buganim Y; Maetzel D; Ng AH; Cassady JP; Cohen MA; Chakraborty S; Wang H; Spooner E; Ploegh H; Gsponer J; Korolchuk VI; Jaenisch R. 2013. Impaired autophagy in the lipid-storage disorder Niemann-Pick type C1 disease. Cell Rep 5(5):1302-15. PubMed: 24290752 MGI: J:206841
Sarna JR; Larouche M; Marzban H; Sillitoe RV; Rancourt DE; Hawkes R. 2003. Patterned Purkinje cell degeneration in mouse models of Niemann-Pick type C disease. J Comp Neurol 456(3):279-91. PubMed: 12528192 MGI: J:81305
Sawamura N; Gong JS; Garver WS; Heidenreich RA; Ninomiya H; Ohno K; Yanagisawa K; Michikawa M. 2001. Site-specific phosphorylation of tau accompanied by activation of mitogen-activated protein kinase (MAPK) in brains of Niemann-Pick type C mice. J Biol Chem 276(13):10314-9. PubMed: 11152466 MGI: J:69686
Seo Y; Kim HS; Kang I; Choi SW; Shin TH; Shin JH; Lee BC; Lee JY; Kim JJ; Kook MG; Kang KS. 2016. Cathepsin S contributes to microglia-mediated olfactory dysfunction through the regulation of Cx3cl1-Cx3cr1 axis in a Niemann-Pick disease type C1 model. Glia 64(12):2291-2305. PubMed: 27687148 MGI: J:236227
Seo Y; Kim HS; Shin Y; Kang I; Choi SW; Yu KR; Seo KW; Kang KS. 2014. Excessive microglial activation aggravates olfactory dysfunction by impeding the survival of newborn neurons in the olfactory bulb of Niemann-Pick disease type C1 mice. Biochim Biophys Acta 1842(11):2193-203. PubMed: 25132229 MGI: J:218464
Shio H; Fowler S; Bhuvaneswaran C; Morris MD. 1982. Lysosome lipid storage disorder in NCTR-BALB/c mice. II. Morphologic and cytochemical studies. Am J Pathol 108(2):150-9. PubMed: 6765732 MGI: J:10213
Sleat DE; Wiseman JA; El-Banna M; Price SM; Verot L; Shen MM; Tint GS; Vanier MT; Walkley SU; Lobel P. 2004. Genetic evidence for nonredundant functional cooperativity between NPC1 and NPC2 in lipid transport. Proc Natl Acad Sci U S A 101(16):5886-91. PubMed: 15071184 MGI: J:89617
Soga M; Ishitsuka Y; Hamasaki M; Yoneda K; Furuya H; Matsuo M; Ihn H; Fusaki N; Nakamura K; Nakagata N; Endo F; Irie T; Era T. 2015. HPGCD outperforms HPBCD as a potential treatment for Niemann-Pick disease type C during disease modeling with iPS cells. Stem Cells 33(4):1075-88. PubMed: 25522247 MGI: J:223979
Speak AO; Te Vruchte D; Davis LC; Morgan AJ; Smith DA; Yanjanin NM; Simmons L; Hartung R; Runz H; Mengel E; Beck M; Imrie J; Jacklin E; Wraith JE; Hendriksz C; Lachmann R; Cognet C; Sidhu R; Fujiwara H; Ory DS; Galione A; Porter FD; Vivier E; Platt FM. 2014. Altered distribution and function of natural killer cells in murine and human Niemann-Pick disease type C1. Blood 123(1):51-60. PubMed: 24235134 MGI: J:208090
Suresh S; Yan Z; Patel RC; Patel YC; Patel SC. 1998. Cellular cholesterol storage in the Niemann-Pick disease type C mouse is associated with increased expression and defective processing of apolipoprotein D. J Neurochem 70(1):242-51. PubMed: 9422368 MGI: J:120242
Suzuki M; Sugimoto Y; Ohsaki Y; Ueno M; Kato S; Kitamura Y; Hosokawa H; Davies JP; Ioannou YA; Vanier MT; Ohno K; Ninomiya H. 2007. Endosomal accumulation of Toll-like receptor 4 causes constitutive secretion of cytokines and activation of signal transducers and activators of transcription in Niemann-Pick disease type C (NPC) fibroblasts: a potential basis for glial cell activation in the NPC brain. J Neurosci 27(8):1879-91. PubMed: 17314284 MGI: J:118352
Takikita S; Fukuda T; Mohri I; Yagi T; Suzuki K. 2004. Perturbed myelination process of premyelinating oligodendrocyte in Niemann-Pick type C mouse. J Neuropathol Exp Neurol 63(6):660-73. PubMed: 15217094 MGI: J:104958
Taylor AM; Liu B; Mari Y; Liu B; Repa JJ. 2012. Cyclodextrin mediates rapid changes in lipid balance in Npc1-/- mice without carrying cholesterol through the bloodstream. J Lipid Res 53(11):2331-42. PubMed: 22892156 MGI: J:190568
Tokoro T; Yamamoto T; Nozaki K; Kusano K; Miyawaki S; Pentchev PG; Maekawa K; Eto Y. 1996. Allelic mutations in two Niemann-Pick disease model mice: SPM (C57BL/KSJ) and NCTR (NCTR-BALB/C) Jikeikai Med J 43:115-21. MGI: J:36039
Tortelli B; Fujiwara H; Bagel JH; Zhang J; Sidhu R; Jiang X; Yanjanin NM; Shankar RK; Carillo-Carasco N; Heiss J; Ottinger E; Porter FD; Schaffer JE; Vite CH; Ory DS. 2014. Cholesterol homeostatic responses provide biomarkers for monitoring treatment for the neurodegenerative disease Niemann-Pick C1 (NPC1). Hum Mol Genet 23(22):6022-33. PubMed: 24964810 MGI: J:214969
Treiber-Held S; Distl R; Meske V; Albert F; Ohm TG. 2003. Spatial and temporal distribution of intracellular free cholesterol in brains of a Niemann-Pick type C mouse model showing hyperphosphorylated tau protein. Implications for Alzheimer's disease. J Pathol 200(1):95-103. PubMed: 12692847 MGI: J:149812
Ulatowski L; Parker R; Davidson C; Yanjanin N; Kelley TJ; Corey D; Atkinson J; Porter F; Arai H; Walkley SU; Manor D. 2011. Altered vitamin E status in Niemann-Pick type C disease. J Lipid Res 52(7):1400-10. PubMed: 21550990 MGI: J:174801
Uronen RL; Lundmark P; Orho-Melander M; Jauhiainen M; Larsson K; Siegbahn A; Wallentin L; Zethelius B; Melander O; Syvanen AC; Ikonen E. 2010. Niemann-Pick C1 modulates hepatic triglyceride metabolism and its genetic variation contributes to serum triglyceride levels. Arterioscler Thromb Vasc Biol 30(8):1614-20. PubMed: 20489167 MGI: J:179556
Vainio S; Bykov I; Hermansson M; Jokitalo E; Somerharju P; Ikonen E. 2005. Defective insulin receptor activation and altered lipid rafts in Niemann-Pick type C disease hepatocytes. Biochem J 391(Pt 3):465-72. PubMed: 15943586 MGI: J:117577
Vazquez MC; del Pozo T; Robledo FA; Carrasco G; Pavez L; Olivares F; Gonzalez M; Zanlungo S. 2011. Alteration of gene expression profile in Niemann-Pick type C mice correlates with tissue damage and oxidative stress. PLoS One 6(12):e28777. PubMed: 22216111 MGI: J:182335
Veyron P; Mutin M; Touraine JL. 1996. Transplantation of fetal liver cells corrects accumulation of lipids in tissues and prevents fatal neuropathy in cholesterol-storage disease BALB/c mice. Transplantation 62(8):1039-45. PubMed: 8900297 MGI: J:36923
Wang MD; Franklin V; Sundaram M; Kiss RS; Ho K; Gallant M; Marcel YL. 2007. Differential regulation of ATP binding cassette protein A1 expression and ApoA-I lipidation by Niemann-Pick type C1 in murine hepatocytes and macrophages. J Biol Chem 282(31):22525-33. PubMed: 17553802 MGI: J:124579
Wang MD; Kiss RS; Franklin V; McBride HM; Whitman SC; Marcel YL. 2007. Different cellular traffic of LDL-cholesterol and acetylated LDL-cholesterol leads to distinct reverse cholesterol transport pathways. J Lipid Res 48(3):633-45. PubMed: 17148552 MGI: J:120283
Wasser CR; Ertunc M; Liu X; Kavalali ET. 2007. Cholesterol-dependent balance between evoked and spontaneous synaptic vesicle recycling. J Physiol 579(Pt 2):413-29. PubMed: 17170046 MGI: J:140844
Weintraub H; Abramovici A; Sandbank U; Pentchev PG; Brady RO; Sekine M; Suzuki A; Sela B. 1985. Neurological mutation characterized by dysmyelination in NCTR-Balb/C mouse with lysosomal lipid storage disease. J Neurochem 45(3):665-72. PubMed: 4031853 MGI: J:7989
Welch CL; Sun Y; Arey BJ; Lemaitre V; Sharma N; Ishibashi M; Sayers S; Li R; Gorelik A; Pleskac N; Collins-Fletcher K; Yasuda Y; Bromme D; D'Armiento JM; Ogletree ML; Tall AR. 2007. Spontaneous atherothrombosis and medial degradation in Apoe-/-, Npc1-/- mice. Circulation 116(21):2444-52. PubMed: 17984379 MGI: J:142987
Williams IM; Wallom KL; Smith DA; Al Eisa N; Smith C; Platt FM. 2014. Improved neuroprotection using miglustat, curcumin and ibuprofen as a triple combination therapy in Niemann-Pick disease type C1 mice. Neurobiol Dis 67:9-17. PubMed: 24631719 MGI: J:213658
Wu YP; Mizukami H; Matsuda J; Saito Y; Proia RL; Suzuki K. 2005. Apoptosis accompanied by up-regulation of TNF-alpha death pathway genes in the brain of Niemann-Pick type C disease. Mol Genet Metab 84(1):9-17. PubMed: 15639190 MGI: J:95531
Xie C; Burns DK; Turley SD; Dietschy JM. 2000. Cholesterol is sequestered in the brains of mice with Niemann-Pick type C disease but turnover is increased. J Neuropathol Exp Neurol 59(12):1106-17. PubMed: 11138930 MGI: J:104996
Xie C; Richardson JA; Turley SD; Dietschy JM. 2006. Cholesterol substrate pools and steroid hormone levels are normal in the face of mutational inactivation of NPC1 protein. J Lipid Res 47(5):953-63. PubMed: 16461760 MGI: J:109000
Xie C; Turley SD; Dietschy JM. 2000. Centripetal cholesterol flow from the extrahepatic organs through the liver is normal in mice with mutated niemann-pick type C protein (NPC1) J Lipid Res 41(8):1278-89. PubMed: 10946016 MGI: J:64028
Xie C; Turley SD; Dietschy JM. 1999. Cholesterol accumulation in tissues of the Niemann-pick type C mouse is determined by the rate of lipoprotein-cholesterol uptake through the coated-pit pathway in each organ. Proc Natl Acad Sci U S A 96(21):11992-7. PubMed: 10518564 MGI: J:76735
Xie C; Turley SD; Pentchev PG; Dietschy JM. 1999. Cholesterol balance and metabolism in mice with loss of function of Niemann-Pick C protein. Am J Physiol 276(2 Pt 1):E336-44. PubMed: 9950794 MGI: J:76733
Xie X; Brown MS; Shelton JM; Richardson JA; Goldstein JL; Liang G. 2011. Amino acid substitution in NPC1 that abolishes cholesterol binding reproduces phenotype of complete NPC1 deficiency in mice. Proc Natl Acad Sci U S A 108(37):15330-5. PubMed: 21896731 MGI: J:176587
Xu S; Chen X; Wei X; Liu G; Wang Q. 2011. Presynaptic impairment in Niemann-Pick C1-deficient neurons: not dependent on presence of glial cells. Neurosci Lett 496(1):54-9. PubMed: 21507342 MGI: J:173215
Xu S; Zhou S; Xia D; Xia J; Chen G; Duan S; Luo J. 2010. Defects of synaptic vesicle turnover at excitatory and inhibitory synapses in Niemann-Pick C1-deficient neurons. Neuroscience 167(3):608-20. PubMed: 20167265 MGI: J:161496
Yadid G; Sotnik-Barkai I; Tornatore C; Baker-Cairns B; Harvey-White J; Pentchev PG; Goldin E. 1998. Neurochemical alterations in the cerebellum of a murine model of Niemann-Pick type C disease. Brain Res 799(2):250-6. PubMed: 9675302 MGI: J:48956
Yan X; Yang F; Lukas J; Witt M; Wree A; Rolfs A; Luo J. 2014. Hyperactive glial cells contribute to axonal pathologies in the spinal cord of Npc1 mutant mice. Glia 62(7):1024-40. PubMed: 24644136 MGI: J:210979
Yevenes LF; Klein A; Castro JF; Marin T; Leal N; Leighton F; Alvarez AR; Zanlungo S. 2012. Lysosomal vitamin E accumulation in Niemann-Pick type C disease. Biochim Biophys Acta 1822(2):150-60. PubMed: 22120593 MGI: J:180321
Yu T; Shakkottai VG; Chung C; Lieberman AP. 2011. Temporal and cell-specific deletion establishes that neuronal Npc1 deficiency is sufficient to mediate neurodegeneration. Hum Mol Genet 20(22):4440-51. PubMed: 21856732 MGI: J:176888
Yu W; Gong JS; Ko M; Garver WS; Yanagisawa K; Michikawa M. 2005. Altered cholesterol metabolism in Niemann-Pick type C1 mouse brains affects mitochondrial function. J Biol Chem 280(12):11731-9. PubMed: 15644330 MGI: J:98011
Yu W; Ko M; Yanagisawa K; Michikawa M. 2005. Neurodegeneration in heterozygous Niemann-Pick type C1 (NPC1) mouse: implication of heterozygous NPC1 mutations being a risk for tauopathy. J Biol Chem 280(29):27296-302. PubMed: 15919659 MGI: J:100816
Zhou S; Davidson C; McGlynn R; Stephney G; Dobrenis K; Vanier MT; Walkley SU. 2011. Endosomal/Lysosomal processing of gangliosides affects neuronal cholesterol sequestration in niemann-pick disease type C. Am J Pathol 179(2):890-902. PubMed: 21708114 MGI: J:174399
te Vruchte D; Lloyd-Evans E; Veldman RJ; Neville DC; Dwek RA; Platt FM; van Blitterswijk WJ; Sillence DJ. 2004. Accumulation of glycosphingolipids in Niemann-Pick C disease disrupts endosomal transport. J Biol Chem 279(25):26167-75. PubMed: 15078881 MGI: J:91039

Also Known As: npcnih

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Control Suggestions

Additional Information

Npc1m1N

Allele Symbol: Npc1m1N

Disease Terms

Research Areas By Genotype

This mouse can be used to support research in many areas including:

Genotype: Npc1m1N related

Mammalian Phenotype Terms by Genotype

Genotype: Npc1m1N/Npc1m1NBALB/c-Npc1m1N

mortality/aging

growth/size/body region phenotype

nervous system phenotype

behavior/neurological phenotype

homeostasis/metabolism phenotype

cellular phenotype

hematopoietic system phenotype

immune system phenotype

liver/biliary system phenotype

Genotype: Npc1m1N/Npc1m1Ninvolves: BALB/c

mortality/aging

nervous system phenotype

cellular phenotype

adipose tissue phenotype

endocrine/exocrine gland phenotype

cardiovascular system phenotype

behavior/neurological phenotype

growth/size/body region phenotype

hematopoietic system phenotype

homeostasis/metabolism phenotype

immune system phenotype

liver/biliary system phenotype

reproductive system phenotype

respiratory system phenotype

Genotype: Npc1m1N/Npc1m1NB6.C-Npc1m1N

nervous system phenotype

hematopoietic system phenotype

homeostasis/metabolism phenotype

cellular phenotype

immune system phenotype

liver/biliary system phenotype

Genotype: Npc1m1N/Npc1m1Ninvolves: 129S1/Sv * BALB/c * C57BL/6

mortality/aging

growth/size/body region phenotype

homeostasis/metabolism phenotype

nervous system phenotype

liver/biliary system phenotype

Genotype: Npc1m1N/Npc1m1Ninvolves: 129S2/SvPas * BALB/c * C57BL/6

mortality/aging

Genotype: Npc1m1N/Npc1m1Ninvolves: BALB/c * C3H/HeJ * C57BL/6J

mortality/aging

behavior/neurological phenotype

nervous system phenotype

hematopoietic system phenotype

homeostasis/metabolism phenotype

immune system phenotype

References

Additional References

Additional - Npc1m1N related

Genotyping Protocols

Dietary Information

Breeding Considerations

Mating System

Appearance

Citation

Animal Health Reports

Live Mouse

Breeder Pair

Cryorecovery - Pricing

Progeny testing is not required

Related Products and Services

Payment Terms and Conditions

The Jackson Laboratory's Genotype Promise

Terms of Use

Also Known As: npc^nih

Npc1^m1N

Allele Symbol: Npc1^m1N

Genotype: Npc1^m1N related

Genotype: Npc1^m1N/Npc1^m1N
BALB/c-Npc1^m1N

Genotype: Npc1^m1N/Npc1^m1N
involves: BALB/c

Genotype: Npc1^m1N/Npc1^m1N
B6.C-Npc1^m1N

Genotype: Npc1^m1N/Npc1^m1N
involves: 129S1/Sv * BALB/c * C57BL/6

Genotype: Npc1^m1N/Npc1^m1N
involves: 129S2/SvPas * BALB/c * C57BL/6

Genotype: Npc1^m1N/Npc1^m1N
involves: BALB/c * C3H/HeJ * C57BL/6J

Additional - Npc1^m1N related