Overview

Also Known As:npc^nih, Niemann Pick type C1 NIH

This strain provides a broadly used model for severe infantile Niemann Pick Type C1, but unlike human NPC1, no neurofibrillary tangles are found. This null allele has a slightly later onset and decreased severity on this BALB background relative to homozygotes on a C57BL/6 congenic background or homozygotes for the Npc1^spm allele on a C57BLKS/J background, but this model is more severe than the C57BL/6J-Npc1^nmf164/J model.

Our preclinical efficacy testing services offer scientific expertise and an array of target-based and phenotype-based outcome measures, both in vivo and at endpoint, for flexible study designs and assay development in mouse models of Niemann Pick Type C. See our full service platform.

Genetic overview

Genetic Background	Generation
	?+F49 (2019-10-03 00:00:00)

Npc1^m1N

Allele Type	Gene Symbol	Gene Name
Spontaneous	Npc1	NPC intracellular cholesterol transporter 1

View Genetics

Research Applications

Mouse/Human Gene Homologs
Neurobiology Research
Sensorineural Research
Reproductive Biology Research
Metabolism Research
Internal/Organ Research
Cardiovascular Research
Immunology, Inflammation and Autoimmunity Research

View All Research Applications

Base Price

Starting at:

$255.00 Domestic price for female

333.51 Domestic price for breeder pair

View Price List

Details

Detailed Description

NPC1 is a transmembrane protein with a sterol-sensing domain that is essential for intracellular transport of unesterified cholesterol out of the endolysosomal compartment to the cytosol. It is primarily localized to late endosomes and lysosomes, but also cycles through the Golgi apparatus. Defects in this gene cause Niemann-Pick Disease Type 1C, in which failed lipid metabolism leads to accumulation of cholesterol and fatty acids in all tissues, with pronounced consequences in spleen, liver, lungs, lymph nodes, thymus, bone marrow and brain. Mice homozygous for the spontaneous Npc1^m1N mutation on the BALB/cNctr background have neuronal accumulation of unesterified cholesterol and gangliosides by birth, develop axonal spheroids beginning at approximately 3 weeks of age, progressive weight loss, progressive cerebellar ataxia with onset beginning at approximately 6 weeks of age, microgliosis, and neurodegeneration that is pronounced in the thalamus and Purkinje cells. Purkinje cells show progressive, patterned degeneration from rostral to caudal beginning with zebrin II negative Purkinje cells. Cerebellar sections showed a normal number of Purkinje cells at 30 days of age, by 50 days most were gone from lobules l-III, and by 70 days they only remained in lobule X, but Bergman glia, oligodendrocytes, and granules cells remained intact in all lobules at 70 days of age (Ko et al., 2005). By 40 days of age the brains of homozygotes are significantly smaller than normal. The average reported lifespan is approximately 9-11 weeks. Loss of glia in the corpus callosum precedes the loss of Purkinje cells, and neuroinflammation in BALB/cNctr-Npc1^m1N/J homozygotes involves atypical microglia (Cougnoux et al., 2018) that are present by 9 days of age and in significant numbers by 22 days of age (Reid et al., 2004). Hypomyelination of the corpus collosum, anterior commissure, and cerebral cortex is found by 10 days of age and progresses, although the optic tract, brainstem, cerebellar white matter, external capsule and optic nerves remain well myelinated. Although premyelinating oligodendrocytes are plentiful at 10 days of age, there is a significant diminution in mature oligodendrocytes at 20 days of age (Takikita et al., 2004). Hyperphosphorylation of tau was found in extracts from BALB/cNctr-Npc1^m1N/J homozygous cerebrum and cerebellum, but no neurofibrillary tangles were detected (Treiber-Held et al., 2003). Hovakimyan et al. (2013) found highly disrupted olfactory epithelium, abnormal olfactory nerve morphology, increased activated microglia in the olfactory epithelium, loss of olfactory neurons and impaired olfactory response to phenylethyl alcohol, hydrogen sulfide, and carbon dioxide in homozygotes by 10 weeks of age, with less severe changes already evident by 35 days of age. Mitochondrial membrane potential and ATP level are lower than normal in tissues from homozygotes, and the mitochondria of the brain are smaller and more rounded than normal with translucent matrices and irregular cisternae. Addition of ATP to culture medium allows the neurite extension and sprouting that is normally diminished in neurons from homozygotes, indicating that the deterioration of neurite outgrowth in homozygous brains stems from inadequate ATP (Yu et al., 2005).

Non-neuronal tissues are also severely affected resulting in hepatosplenomegaly, micronodularity and increased mass of the lungs, and reproductive defects. Histology of the lung of homozygotes on a BALB/c background at 70 days of age found thickened intra-alveolar septae, enlarged lamellar bodies in type II pneumocytes, accumulation of surfactant with increased phospholipid and cholesterol content, and clusters of large foamy alveolar macrophages and vacuolar-filled leukocytes (Roszell et al., 2013). Npc1^m1N homozygous females are infertile, with underdeveloped ovarian follicles, but transplanting ovaries from homozygotes to wild-type hosts permits ovulation and formation of corpora lutea (Gevry et al., 2004). On this BALB background homozygous males are also infertile and fail to fertilize even zona-free eggs in IVF (Fan et al., 2006), although males on a mixed BALB x 129 background are reportedly fertile (Erickson et al., 2002). Npc1^m1N/+ heterozygotes on this BALB/cNctr background have also been found to display elevated cholesterol levels and decreased ATP in the cerebrum and cerebellum, loss of 25-30% of Purkinje cells, and hyperphosphorylation of tau all in very old mice, 104-106 weeks of age, but not at 24 or 40 weeks of age (Yu et al., 2005).

This model of the Niemann-Pick Type C1 lysosomal storage disease is an early onset model that is more severe than the Npc1^nmf164 model but less severe than when this Npc1^m1N allele is backcrossed to congenicity onto the C57BL/6 background. Metabolomic profiles from liver extracts of homozygotes at 49 days of age showed a more significant increase in accumulation of ceramides, sphingomyelins, sphingoid bases, gangliosides, free cholesterol, and oxysterols on the congenic C57BL/6J background relative to homozygotes on a BALB/c background. The impact of genetic background was less severe in brain metabolomic profiles in which congenic C57BL/6J homozygotes accumulate more ceramide, lactosylceramide, and 3B,5a,6B-cholestan-triol compared with homozygotes on the BALB/c background (Praggastis et al., 2015). Axonal spheroids are highly concentrated in the fimbria on the C57BL/6 congenic background (Walkley and Suzuki, 2004). The Npc1^m1N allele is a null allele; Western blot of liver extracts from homozygotes at 30 and 75 days of age failed to detect NPC1 protein, whereas small amounts of NPC1 were identified in Npc1^nmf164 homozygotes at each timepoint assessed between 30 and 120 days of age (Maue et al., 2011). Purkinje cell loss at 6 weeks of age in Npc1^nm1N homozygotes was reported to be equivalent to the loss found at 9 weeks of age in Npc1^nmf164 homozygotes (Maue et al., 2011) and the demyelination phenotype is less severe in Npc1^nnmf164 homozygotes. Npc1^nmf164 homozygotes have bred before becoming debilitated, but Npc1^m1N must be maintained from heterozygous breeders. The C57BLKS/J-Npc1^spm/J model displays a faster, more severe Purkinje cell loss than do these Npc1^m1N homozygotes on the BALB/c background, but survive approximately 15 days longer than this model (Sarna et al., 2003).

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; lcsd; lysosomal cholesterol storage disease; nctr; NPC; Npc-; npc^nih; NPC1; NPC1-; Npc1^N; npc1^NIH
Gene Symbol and Name	Npc1, NPC intracellular cholesterol transporter 1
Gene Synonym(s)
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

Models with phenotypic similarity to human diseases where etiology is unknown or involving genes where ortholog is unknown.

Niemann-Pick disease

Research Areas By Phenotype

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

Genotype: Npc1^m1N related

Mouse/Human Gene Homologs
- Niemann-Pick disease, type C
Neurobiology Research
- Cerebellar Defects
- Metabolic Defects
- Myelination Defects
- Neurodegeneration
- Neuromuscular defects
- Tremor Defects
- Ataxia (Movement) Defects
Metabolism Research
Internal/Organ Research
- Liver Defects
- Spleen Defects

Sensorineural Research
- Olfaction
Reproductive Biology Research
- Fertility Defects
Neurobiology Research
- Myelination Defects
- Neurodegeneration
- Tremor Defects
- Neuromuscular defects
- Ataxia (Movement) Defects
- Cerebellar Defects
- Metabolic Defects
Cardiovascular Research
Immunology, Inflammation and Autoimmunity Research
- Lymphoid Tissue Defects
Internal/Organ Research
- Lung Defects
Metabolism Research
Research Tools
- Metabolism Research

Mammalian Phenotype Terms by Genotype

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

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

growth/size/body region phenotype

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

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

mortality/aging

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

nervous system phenotype

Purkinje cell degeneration

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
- galactosylceramide levels were reduced in the brain, reflecting a general loss of myelin lipids
- -GM2
- 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

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
B6.C-Npc1

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

nervous system phenotype

astrocytosis

microgliosis

Purkinje cell degeneration
- at 7 weeks

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

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

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

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

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

nervous system phenotype

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
- Normal - 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

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
- Normal - 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

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
- Normal - 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

The following phenotype relates to a compound genotype created using this strain

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

adipose tissue phenotype

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

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
- Normal - 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

abnormal sperm physiology
- 30% of total cyritestin protein is not proteolytically processed on mutant cauda sperm, whereas fertilin beta is processed normally

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 binding of sperm to zona pellucida
- 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
- 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

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

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
- Normal - 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
- Normal - 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

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

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

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

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

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

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

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

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

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
- Normal - 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
- Normal - in contrast, pituitary expression and circulating levels of GH remain unaffected

lipidosis
- 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

cellular phenotype

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

abnormal Golgi apparatus morphology
- Golgi fragmentation is found in neurons of the cerebral cortex, cerebellar Purkinje cells, and brainstem neurons

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

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)

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

mortality/aging

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

nervous system phenotype

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

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

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

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

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
- Normal - 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 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

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

small cerebellum
- cerebellum weight is smaller than controls

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

behavior/neurological phenotype

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

cellular phenotype

abnormal primary cilium morphology
- analysis at postnatal day 12 finds slightly fewer ACIII stained hippocampal neurons, indicative of fewer neurons having a primary cilium, and immuno-electron microscopy shows that these cilia are also shorter than those of wild-type controls

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
- 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

increased microglial cell activation
- age dependent increase in microglial activity

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

mortality/aging

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

nervous system phenotype

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

abnormal Purkinje cell dendrite morphology

abnormal Purkinje cell morphology
- focal axonal swellings are found in Purkinje cells of the cerebellar and vestibular nuclei, the granular layer, and the white matter tracts, an accumulation of vesicular storage material in the cytoplasm of the somata is evident beginning between 4 and 8 weeks of age, dendritic arbors and thick megadendrites are also found and Purkinje cell axonal swellings are common in the granule layer
- polymembranous storage bodies are found in lobule X Purkinje cells from P63 mice

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

increased microglial cell activation
- age dependent increase in microglial activity

Purkinje cell degeneration
- at 35 days of age Purkinje cell loss is not found, but by 45 days of age there is loss of zebrin II negative Purkinje cells throughout the cerebellum in a banded pattern which has bands of surviving Purkinje cells, but the posterior cerebellum only has some gaps in the molecular layer, especially in the hemispheres; at 60 days of age patterned Purkinje cell loss is clear in the posterior hemispheres and the anterior lobe of the cerebellum shows loss in bot the vermis and hemispheres, but the nodular zone and lobule X are resistant to this Purkinje cell loss.
- 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

growth/size/body region phenotype

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

hematopoietic system phenotype

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

abnormal microglial cell activation
- 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

increased microglial cell activation
- age dependent increase in microglial activity

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
- cholesterol accumulation within cell bodies and axonal segments of neocortical neurons
- Background Sensitivity - decreased accumulation in P49 liver tissue as compared to C57BL/6 background, but level is higher than control
- 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

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):887-903PubMed: 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):5645-9PubMed: 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):1154-63PubMed: 12437586 MGI: J:80447
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):257-63PubMed: 7202025 MGI: J:6833
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):465-8PubMed: 6315811 MGI: J:7245
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):379-84PubMed: 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):140-9PubMed: 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):669-79PubMed: 6257302 MGI: J:18511
Vivas O; Tiscione SA; Dixon RE; Ory DS; Dickson EJ. 2019. Niemann-Pick Type C Disease Reveals a Link between Lysosomal Cholesterol and PtdIns(4,5)P2 That Regulates Neuronal Excitability. Cell Rep 27(9):2636-2648.e4PubMed: 31141688 MGI: J:278830
Xie C; Gong XM; Luo J; Li BL; Song BL. 2017. AAV9-NPC1 significantly ameliorates Purkinje cell death and behavioral abnormalities in mouse NPC disease. J Lipid Res 58(3):512-518PubMed: 28053186 MGI: J:274490

Additional - Npc1^m1N related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Separated PCR:Npc1
- Standard PCR:Npc1Alternate1
- Separated MCA:Npc1
- Genotyping resources and troubleshooting
Dietary Information
- LabDiet® 5K52 formulation (6% fat)
Breeding Considerations

When maintaining a live colony, heterozygous mice may be intercrossed or bred to wildtype siblings. Homozygotes are sterile.
- Additional Breeding and Husbandry Support
Mating System
- Wild-type x Heterozygote
- Heterozygote x Wild-type
Appearance
- albino, ataxic, tremors
  Related Genotype: a/a Tyrp1^b/Tyrp1^b Tyr^c/Tyr^c Npc1^m1N/Npc1^m1N
  
  albino, unaffected
  Related Genotype: a/a Tyrp1^b/Tyrp1^b Tyr^c/Tyr^c Npc1^m1N/+ or +/+
Citation
When using the Niemann Pick type C1 NIH mouse strain in a publication, please cite the originating article(s) and include JAX stock #003092 in your Materials and Methods section.

Animal Health Reports

Facility Barrier Level Descriptions

FGB29 (Standard)

Pricing & Availability

Available

Domestic
International

Live Mouse

Age

Genotype

Price

weeks

Breeder Pair

Sex

Genotype

Price

Female
Male

Cryorecovery - Pricing

Service/Product	Description	Price
	Heterozygous or Wild-type for Npc1<m1N>

Payment Terms and Conditions

Terms are granted by individual review and stated on the customer invoice(s) and account statement. These transactions are payable in U.S. currency within the granted terms. Payment for services, products, shipping containers, and shipping costs that are rendered are expected within the payment terms indicated on the invoice or stated by contract. Invoices and account balances in arrears of stated terms may result in The Jackson Laboratory pursuing collection activities including but not limited to outside agencies and court filings.

The Jackson Laboratory's Genotype Promise

The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project. We do not guarantee breeding performance and therefore suggest that investigators order more than one breeding pair to avoid delays in their research.

Terms Of Use

General Terms and Conditions

Questions about Terms of Use

Licensing Information

Phone: 207-288-6470

Email: TechTran@jax.org

JAX® Mice, Products & Services Conditions of Use

"MICE" means mouse strains, their progeny derived by inbreeding or crossbreeding, unmodified derivatives from mouse strains or their progeny supplied by The Jackson Laboratory ("JACKSON"). "PRODUCT(S)" means biological materials supplied by JACKSON, and their derivatives. "SERVICES" means projects conducted by JACKSON for other parties that may include but are not limited to the use of MICE or PRODUCTS. "RECIPIENT" means each recipient of MICE, PRODUCTS, or SERVICES provided by JACKSON including each institution, its employees and other researchers under its control. MICE or PRODUCTS shall not be: (i) used for any purpose other than internal research, (ii) sold or otherwise provided to any third party for any use, or (iii) provided to any agent or other third party to provide breeding or other services. Acceptance of MICE, PRODUCTS or SERVICES from JACKSON shall be deemed as agreement by RECIPIENT to these conditions, and departure from these conditions requires JACKSON’s prior written authorization.

No Warranty

MICE, PRODUCTS AND SERVICES ARE PROVIDED "AS IS". JACKSON EXTENDS NO WARRANTIES OF ANY KIND, EITHER EXPRESS, IMPLIED, OR STATUTORY, WITH RESPECT TO MICE, PRODUCTS OR SERVICES, INCLUDING ANY IMPLIED WARRANTY OF MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE, OR ANY WARRANTY OF NON-INFRINGEMENT OF ANY PATENT, TRADEMARK, OR OTHER INTELLECTUAL PROPERTY RIGHTS.

Credit for PRODUCTS or SERVICES

In case of dissatisfaction for a valid reason and claimed in writing by a purchaser within ninety (90) days of receipt of, PRODUCTS or SERVICES, JACKSON will, at its option, provide credit or replacement for the PRODUCT received or the SERVICES provided; JACKSON makes no other representations and this shall be the exclusive remedy of the purchaser. Please note specific policy for live mice.

Animal Care and Use for SERVICES

Consistent with the requirement for a written understanding regarding animal care and use, the JACKSON Animal Care and Use Committee will review the animal care and use protocol(s) associated with any SERVICES to be performed at JACKSON, and JACKSON shall have ultimate responsibility and authority for the care of animals while on site or in JACKSON custody.

No Liability

In no event shall JACKSON, its trustees, directors, officers, employees, and affiliates be liable for any causes of action or damages, including any direct, indirect, special, or consequential damages, arising out of the provision of MICE, PRODUCTS, or SERVICES, including economic damage or injury to property and lost profits, and including any damage arising from acts or negligence on the part of JACKSON, its agents or employees. Unless prohibited by law, in purchasing or receiving MICE, PRODUCTS, or SERVICES from JACKSON, purchaser or recipient, or any party claiming by or through them, expressly releases and discharges JACKSON from all such causes of action or damages, and further agrees to defend and indemnify JACKSON from any costs or damages arising out of any third party claims.

MICE, PRODUCTS or SERVICES are to be used in a safe manner and in accordance with all applicable governmental rules and regulations.

The foregoing represents the General Terms and Conditions applicable to JACKSON’s MICE, PRODUCTS or SERVICES. In addition, special terms and conditions of sale of certain MICE, PRODUCTS, or SERVICES may be set forth separately in JACKSON web pages, catalogs, price lists, contracts, and/or other documents, and these special terms and conditions shall also govern the sale of these MICE, PRODUCTS and SERVICES by JACKSON, and by its licensees and distributors.

Acceptance of delivery of MICE, PRODUCTS or SERVICES shall be deemed agreement to these terms and conditions. No purchase order or other document transmitted by purchaser or recipient that may modify the terms and conditions hereof, shall be in any way binding on JACKSON, and instead the terms and conditions set forth herein, including any special terms and conditions set forth separately, shall govern the sale of MICE, PRODUCTS or SERVICES by JACKSON.

Also Known As:npcnih, Niemann Pick type C1 NIH

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Control Suggestions

Additional Information

Npc1m1N

Allele Symbol: Npc1m1N

Disease Terms

Models with phenotypic similarity to human diseases where etiology is unknown or involving genes where ortholog is unknown.

Research Areas By Phenotype

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

Genotype: Npc1m1N related

Mammalian Phenotype Terms by Genotype

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

growth/size/body region phenotype

liver/biliary system phenotype

mortality/aging

nervous system phenotype

homeostasis/metabolism phenotype

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

mortality/aging

Genotype: Npc1m1N/Npc1m1NB6.C-Npc1

cellular phenotype

immune system phenotype

liver/biliary system phenotype

nervous system phenotype

hematopoietic system phenotype

homeostasis/metabolism phenotype

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

behavior/neurological phenotype

immune system phenotype

mortality/aging

nervous system phenotype

hematopoietic system phenotype

homeostasis/metabolism phenotype

Genotype: Npc1m1N/Npc1m1Ninvolves: BALB/c

adipose tissue phenotype

reproductive system phenotype

endocrine/exocrine gland phenotype

respiratory system phenotype

behavior/neurological phenotype

growth/size/body region phenotype

hematopoietic system phenotype

cardiovascular system phenotype

homeostasis/metabolism phenotype

cellular phenotype

immune system phenotype

liver/biliary system phenotype

mortality/aging

nervous system phenotype

Genotype: Npc1m1N/Npc1m1NBALB/c-Npc1

behavior/neurological phenotype

cellular phenotype

immune system phenotype

liver/biliary system phenotype

mortality/aging

nervous system phenotype

growth/size/body region phenotype

hematopoietic system phenotype

homeostasis/metabolism 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

Payment Terms and Conditions

The Jackson Laboratory's Genotype Promise

Terms Of Use

Licensing Information

Also Known As:npc^nih, Niemann Pick type C1 NIH

Npc1^m1N

Allele Symbol: Npc1^m1N

Genotype: Npc1^m1N related

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
B6.C-Npc1

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

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

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

Additional - Npc1^m1N related