Overview

These BALB.LDLR knock-out mice may be useful for studying the effects of hyperlipidemia and hyperglycemia on diabetic nephrology and artherosclerosis.

Donating Investigator

Dr. Renee C LeBoeuf, Universtiy of Washington

Genetic overview

Genetic Background	Generation

Ldlr^tm1Her

Allele Type	Gene Symbol	Gene Name
Targeted (Null/Knockout)	Ldlr	low density lipoprotein receptor

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Research Applications

Cardiovascular Research
Mouse/Human Gene Homologs
Metabolism Research
Diabetes and Obesity Research
Internal/Organ Research

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Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

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Details

Detailed Description

In the BALB.LDLR^-/- strain, a neomycin (neo) selection cassette is inserted in exon 4 of the low density lipoprotein receptor (Ldlr) gene, abolishing endogenous gene function. Homozygous mice are viable, fertile, appear normal in size, and do not display any gross physical or behavioral abnormalities. On a 4% diet, BALB.LDLR^-/- mice have increased cholesterol (~200 mg/dl), increased triglycerides (~170mg/dl), and increased blood glucose (122 mg/dl) as compared with wildtype (WT). When moved onto a 21% fat diet these mice have cholesterol levels of 572 mg/dl, triglyceride levels of 180mg/dl, and blood glucose levels of 141 mg/dl. They exhibit renal injury, tubulointerstitial injury, and an increase in interstitial macrophages, and an increase in blood urea nitrogen when challenged with hyperlipidemia and hyperglycemia. When injected with Streptozotocin these mice also exhibit atherosclerotic lesions, aortic sinus lesions, and aortic fatty streak lesions caused by hyperlipidemia. These mice may be useful for studying the effects of hyperlipidemia and hyperglycemia on diabetic nephrology and artherosclerosis.

Development

A targeting vector was designed to insert neomycin (neo) selection cassette into exon 4 of the low density lipoprotein receptor (Ldlr) gene, abolishing gene function. This construct was electroporated into 129S7/SvEvBrd-Hprt1⁺-derived AB-1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts and chimeric males were bred with C57BL/6 females. The resulting offspring were backcrossed to C57BL/6 for at least 10 generations to establish a colony of Ldlr^-/- mice (Stock No. 002207). These mice were subsequently backcrossed to BALB/cByJ for at least 10 generations to establish a colony of BALB.LDLR^-/- mice. Upon arrival at The Jackson Laboratory, mice were bred with BALB/cByJ inbred mice (Stock No. 001026) for at least one generation to establish the colony.

Control Suggestions

Approximate Controls

001026 BALB/cByJ

Additional Information

Considerations for Choosing Controls

Selected References

Ishibashi S; Brown MS; Goldstein JL; Gerard RD; Hammer RE; Herz J. 1993. Hypercholesterolemia in low density lipoprotein receptor knockout mice and its reversal by adenovirus-mediated gene delivery [see comments] J Clin Invest 92(2):883-93PubMed: 8349823 MGI: J:37394

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Genetics

Ldlr^tm1Her

Allele Symbol: Ldlr^tm1Her

Allele Name	targeted mutation 1, Joachim Herz
Allele Type	Targeted (Null/Knockout)
Allele Synonym(s)	LDLR-; LDLR KO; LDLr0; LDLrKO; LDLr-KO; Ldlrtm1Her
Gene Symbol and Name	Ldlr, low density lipoprotein receptor
Gene Synonym(s)
Site of Expression	Immunoblot analysis of liver membranes detected a truncated protein in homozygous mutant animals.
Strain of Origin	129S7/SvEvBrd-Hprt⁺
Chromosome	9
General Note	When used in bone marrow transplant into Ldlr^tm1Her homozygous mice, Abca1^tm1Jdm Abcg1^tm1Dgen homozygous cells accelerate the development of atherosclerosis. (J:130777) Phenotypic Similarity to Human Syndrome: Atherosclerosis, Susceptibility to J:29950, J:225091 in mice fed a high-cholesterol diet.
Molecular Note	Insertion of a neomycin resistance cassette into exon 4. The authors predict that the targeted allele would encode a truncated non-functional protein that will not bind LDL, and that lacks a membrane spanning segment. Immunoblot analysis of liver membranes detected a truncated protein in homozygous mutant animals.
Mutations Made By	Dr. Joachim Herz, Univ of Texas Southwest Med Ctr Dallas

Disease/Phenotype

Disease Terms

Model with phenotypic similarity to human disease where etiologies involve orthologs. Human genes are associated with this disease. Orthologs of those genes appear in the mouse genotype(s).

familial hypercholesterolemia

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

fatty liver disease

Research Areas By Phenotype

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

Genotype: Ldlr^tm1Her related

Cardiovascular Research
- Hypercholesterolemia
- Atherosclerosis
Mouse/Human Gene Homologs
- hypercholesterolemia, familial
Metabolism Research
- Lipid Metabolism

Diabetes and Obesity Research
- Hyperinsulinemia
  - diet-induced
- Hyperglycemia
Metabolism Research
- Lipid Metabolism
Internal/Organ Research
- Kidney Defects
  - Renal tubulointerstitial lesions
Cardiovascular Research
- Hypercholesterolemia

Mammalian Phenotype Terms by Genotype

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

Genotype: Ldlr^tm1Her/Ldlr^tm1Her
involves: 129S7/SvEvBrd * C57BL/6

behavior/neurological phenotype

abnormal short term spatial reference memory
- mice fed a Western diet and tested in a T-maze demonstrate reduced alternation returning more frequently to the blind arm of the maze

abnormal spatial learning
- less time spent in the target quadrant during a probe test
- less time spent in the target quadrant during a probe test
- mice on a Western diet fail to show improved performance over time in a Morris water maze test
- somewhat slower swimming speed in the acquisition phase of a Morris water maze test

cellular phenotype

increased hepatocyte apoptosis
- DD diet fed mice show some apoptotic cells in the liver while those on the DDC diet have a larger increase

maternal effect
- also reduced birth weight persisting to at least 90 days of age
- intrauterine growth restriction of pups from mothers on a high fat diet
- offspring with larger atherosclerotic lesions
- offspring with lower gonadal fat pad to body weight ratio
- poor survival of pups from mothers on a high fat diet

oxidative stress
- mice on the DDC diet exhibit an increase in hepatic oxidative stress

growth/size/body region phenotype

decreased lean body mass

increased liver weight
- mice on the DD diet and on the DDC diet exhibit higher liver weights than regular chow-fed mice

obese
- mice fed a diabetogenic high fat diet (35.5% carbohydrate and 36.6% fat) (DD diet) or a a diabetogenic high fat diet (35.5% carbohydrate and 36.6% fat) with 0.15% added cholesterol (DDC diet) exhibit weight gain leading to obesity; similar weight gain is seen regardless of diet
- seen regardless of diet

hematopoietic system phenotype

abnormal microglial cell morphology
- 2X as many arterioles have microglia
- on a Western diet, even small arterioles have associated microglia, sometimes within the basal lamina

homeostasis/metabolism phenotype

abnormal circulating amino acid level
- Normal - levels of other amino acids are normal
- mothers on a high fat diet have reduced plasma concentrations of phenylalanine, lysine, valine, isoleucine, and leucine

abnormal glucose homeostasis

decreased circulating corticosterone level
- levels in response to ACTH are significantly reduced

impaired glucose tolerance
- 30 minute insulin levels elevated
- glucose levels increase during a glucose tolerance test

increased circulating alanine transaminase level
- ALT levels are increased in mice fed the DD diet and even more so in those fed the DDC diet

increased circulating cholesterol level
- similar levels of hypercholesterolemia are seen in mice fed the DD diet and those fed the DDC diet

increased circulating free fatty acid level
- circulating fatty free acids are increased in mice fed the DD or the DDC diet, however levels are higher in the mice on the DDC diet

increased circulating glucose level
- increased fasting glucose levels after dexamethasone treatment

increased circulating insulin level
- after dexamethasone treatment

increased circulating LDL cholesterol level
- clearance of ¹²⁵I-LDL from circulation is retarded, uptake of DiI-LDL by hepatocytes is decreased, and uptake of ³H-CE-LDL by the liver is lower compared to wild-type

increased circulating triglyceride level
- similar levels of hypertriglyceridemia are seen in mice fed the DD diet and those fed the DDC diet

increased liver cholesterol level
- hepatic cholesterol levels are increased only in the mice fed the DDC diet

increased liver triglyceride level
- hepatic triglyceride levels are increased in mice fed the DD or the DDC diet, but higher in those on the DDC diet

insulin resistance
- less likely to become hypoglycemic during an insulin tolerance test

immune system phenotype

abnormal microglial cell morphology
- 2X as many arterioles have microglia
- on a Western diet, even small arterioles have associated microglia, sometimes within the basal lamina

liver inflammation
- inflammatory cell foci is seen to a greater extend in the livers of mice fed the DDC diet than the DD diet

liver/biliary system phenotype

hepatic steatosis
- mice fed the DDC diet exhibit both macrovesicular and microvesicular steatosis in the liver

increased hepatocyte apoptosis
- DD diet fed mice show some apoptotic cells in the liver while those on the DDC diet have a larger increase

increased liver cholesterol level
- hepatic cholesterol levels are increased only in the mice fed the DDC diet

increased liver triglyceride level
- hepatic triglyceride levels are increased in mice fed the DD or the DDC diet, but higher in those on the DDC diet

increased liver weight
- mice on the DD diet and on the DDC diet exhibit higher liver weights than regular chow-fed mice

liver fibrosis
- intrasinusoidal and pericellular fibrosis is seen to a greater extend in the livers of mice fed the DDC diet than the DD diet

liver inflammation
- inflammatory cell foci is seen to a greater extend in the livers of mice fed the DDC diet than the DD diet

macrovesicular hepatic steatosis
- mice fed the DD diet exhibit diffuse macrovesicular steatosis with limited inflammation and fibrosis in the liver
- mice fed the DDC diet exhibit both macrovesicular and microvesicular steatosis in the liver

microvesicular hepatic steatosis
- mice fed the DDC diet exhibit both macrovesicular and microvesicular steatosis in the liver

nervous system phenotype

abnormal hippocampus morphology
- reduced cell proliferation in the hippocampus

abnormal microglial cell morphology
- 2X as many arterioles have microglia
- on a Western diet, even small arterioles have associated microglia, sometimes within the basal lamina

abnormal synapse morphology
- 32% of the cholesterol in the synaptic plasma membrane is in the exofacial leaflet as compared to 15% for controls
- cholesterol levels in the cytofacial leaflet are reduced
- cholesterol/phospholipid ratio in the synaptic plasma membrane is elevated
- fluidity of both the exofacial leaflet and the cytofacial leaflet of the synaptic plasma membrane are increased relative to controls

abnormal synaptic bouton morphology
- Normal - normal density of synaptophysin-immunoreactive presynaptic boutons in the dentate gyrus
- reduced density of synaptophysin-immunoreactive presynaptic boutons in the CA1 of the hippocampus

photoreceptor outer segment degeneration
- mild degeneration

pigmentation phenotype

abnormal retinal pigment epithelium morphology
- basal membrane infoldings are less regular
- decreased and irregular height
- numerous vacuoles in cytoplasm

vision/eye phenotype

abnormal Bruch membrane morphology
- enhanced condensation of collagenous and elastic fibers
- laminations disrupted and large vacuoles become diffusely distributed
- thickened (up to 0.8um on a high fat diet)

abnormal choriocapillaris morphology
- narrowing of lumina
- reduced number of fenestrations
- thickened endothelial basal lamina

abnormal retinal pigment epithelium morphology
- basal membrane infoldings are less regular
- decreased and irregular height
- numerous vacuoles in cytoplasm

photoreceptor outer segment degeneration
- mild degeneration

cardiovascular system phenotype

abnormal arteriole morphology
- wall thickness increases on a Western diet
- wall thickness is directly related to the number of associated microglia
- wall thickness of brain arterioles having a lumen diameter of 15-40 um is greater than controls

abnormal choriocapillaris morphology
- narrowing of lumina
- reduced number of fenestrations
- thickened endothelial basal lamina

Genotype: Ldlr^tm1Her/Ldlr^tm1Her
involves: 129S7/SvEvBrd

cardiovascular system phenotype

atherosclerotic lesions
- mice develop atherosclerotic lesions after 20 weeks on Western diet
- total lesion area is larger when compared to lesion area in transgenic Tg(Alb-MYLIP*)1Pton mice after 30 weeks on Western diet

increased susceptibility to atherosclerosis

homeostasis/metabolism phenotype

abnormal circulating cholesterol level
- circulating VLDL/LDL cholesterol levels are increased compared to in Apobec1^tm1Chan homozygotes and wild-type mice

abnormal circulating LDL cholesterol level
- LDL clearance is slowed

increased circulating cholesterol level
- increased plasma cholesterol levels after 20 weeks on Western diet
- levels are higher than those exhibited by in transgenic Tg(Alb-MYLIP*)1Pton mice after 30 weeks on Western diet
- plasma cholesterol level is 196mg/dl on a normal diet
- when fed a chow diet or Western-type diet for 2 and 4 weeks, mice exhibit increased serum cholesterol levels compared to in Apobec1^tm1Chan homozygotes and wild-type mice

increased circulating LDL cholesterol level
- in wild-type mice parabiosed with Ldlr-null mice (resulting in shared circulation), plasma total cholesterol levels did not increase significantly over pre-surgery levels
- male mice have a marked increase in plasma LDL cholesterol compared to wild-type
- on a chow diet, plasma LDL levels were higher than both those of wild-type mice and Ldlrap1^tm1Her homozygous mutant mice
- plasma LDL levels become further elevated on high cholesterol diets
- plasma levels are increased 2.5 fold relative to controls

increased circulating triglyceride level
- when fed a chow diet or a Western-type diet for 2 and 4 weeks, mice exhibit increased serum triglyceride levels compared to in Apobec1^tm1Chan homozygotes and wild-type mice

Genotype: Ldlr^tm1Her/Ldlr^tm1Her
involves: 129S6/SvEvTac * 129S7/SvEvBrd * C57BL/6

cardiovascular system phenotype

atherosclerotic lesions
- atherosclerosis in both aortic arch and descending aorta

homeostasis/metabolism phenotype

increased circulating cholesterol level
- hypercholesterolemic

Genotype: Ldlr^tm1Her/Ldlr^tm1Her
B6.129S7-Ldlr

adipose tissue phenotype

abnormal fat pad morphology
- increased when fed a western style diet for 12 weeks

increased percent body fat/body weight
- when fed a western style diet for 12 weeks

growth/size/body region phenotype

decreased susceptibility to weight gain
- lower body weight on a low cholesterol diet than controls on any diet

increased susceptibility to weight gain
- when fed a western style diet for 12 weeks

hematopoietic system phenotype

abnormal microglial cell morphology
- increased number of microglia in the hippocampus

homeostasis/metabolism phenotype

abnormal circulating cholesterol level
- streptozotocin (STZ) induced diabetes leads to blood cholesterol levels that are twice those of non-diabetic mice 6 weeks post-induction and three times greater 8 weeks post- induction
- when fed a western style diet for 12 weeks, male mice exhibit a higher circulating cholesterol level than in Ldlr^tm1Her Scd1^ab-2J homozygotes

abnormal triglyceride level

amyloid beta deposits
- increased amyloid beta 40 but not amyloid beta 42 on a high fat diet

decreased circulating HDL cholesterol level
- when fed a high-cholesterol diet, NMR proton spectra of lipids indicates a level of photon intensity for HDL of 0.77 compared to 0.83 in wild-type mice

decreased circulating interleukin-10 level

hyperglycemia
- streptozotocin (STZ) treatment leads to 3-fold higher level of blood glucose in mice fed a high fat diet
- these high glucose levels persist for at least 12 weeks after STZ treatment
- when fed a western style diet for 12 weeks

impaired glucose tolerance
- when fed a western style diet for 12 weeks

increased circulating cholesterol level
- 10 fold increase in total cholesterol on a high fat diet compared to a 150% increase for controls
- 3 fold cholesterol elevation on a normal diet relative to controls
- mice develop severe cholesterolemia when receiving a high fat diet from 6 to 30 weeks (elevated levels are detected at 6, 15, and 30 weeks)
- seen at 3-4 months of age

increased circulating HDL cholesterol level
- slightly elevated at 3 and 8 months of age

increased circulating insulin level
- when fed a western style diet for 12 weeks

increased circulating interleukin-1 beta level

increased circulating interleukin-6 level

increased circulating LDL cholesterol level
- when fed a high cholesterol diet, NMR proton spectra of lipids indicates a level of photon intensity for LDL of 0.88 compared to 0.84 in wild-type mice

increased circulating triglyceride level
- elevated on a high fat diet
- seen at 3-4 months of age
- when fed a western style diet for 12 weeks, female mice exhibit a higher circulating triglyceride level than in Ldlr^tm1Her Scd1^ab-2J homozygotes

increased circulating tumor necrosis factor level
- increased TNFalpha levels

increased circulating VLDL cholesterol level
- compared to in Ldlr^tm1Her Scd1^ab-2J homozygotes when fed a western style diet for 12 weeks
- when fed a high cholesterol diet, NMR proton spectra of lipids indicates a level of photon intensity for VLDL of 0.92 compared to 0.88 in wild-type mice

increased circulating VLDL triglyceride level
- compared to in Ldlr^tm1Her Scd1^ab-2J homozygotes when fed a western style diet for 12 weeks

increased liver cholesterol level
- livers exhibit slightly, but significantly, higher levels of cholesterol

increased liver triglyceride level
- when fed a western style diet for 12 weeks, mice exhibit a 5-fold higher hepatic triglyceride level than in Ldlr^tm1Her Scd1^ab-2J homozygotes

behavior/neurological phenotype

abnormal spatial learning
- take longer to reach the target site in a Morris water maze when fed a high cholesterol diet

abnormal spatial working memory
- deficient performance in a water radial arm maze regardless of the diet

hyperactivity
- travel greater distances and spend more time in motion in an open field test

increased grip strength
- perform better than controls on a hanging bar test

immune system phenotype

abnormal microglial cell morphology
- increased number of microglia in the hippocampus

decreased circulating interleukin-10 level

increased circulating interleukin-1 beta level

increased circulating interleukin-6 level

increased circulating tumor necrosis factor level
- increased TNFalpha levels

liver/biliary system phenotype

hepatic steatosis
- when fed a western style diet for 12 weeks

increased liver cholesterol level
- livers exhibit slightly, but significantly, higher levels of cholesterol

increased liver triglyceride level
- when fed a western style diet for 12 weeks, mice exhibit a 5-fold higher hepatic triglyceride level than in Ldlr^tm1Her Scd1^ab-2J homozygotes

nervous system phenotype

abnormal astrocyte morphology
- further increase in reactive astrocytes on a high fat diet
- increased numbers of reactive astrocytes

abnormal CNS glial cell morphology

abnormal microglial cell morphology
- increased number of microglia in the hippocampus

amyloid beta deposits
- increased amyloid beta 40 but not amyloid beta 42 on a high fat diet

cardiovascular system phenotype

atherosclerotic lesions

increased susceptibility to atherosclerosis
- 4 weeks on the Western diet mice have lesions of small fatty streaks on the aorta
- after 12 weeks on a high cholesterol diet, mice exhibit endothelial disruption and an accumulation of macrophage and foam cells at the site of atherosclerotic plaques
- after 12 weeks on a high cholesterol diet, mice exhibit extensive intimal thickening and 60% to 80% of the aortic surface is sudanophilic unlike in wild-type mice
- high-fat diet leads to atherosclerosis
- STZ-induced diabetes leads to an almost 3-fold greater size in total lesion area in the aorta compared to non-diabetic Ldlr^tm1Her homozyogotes

Genotype: Ldlr^tm1Her/Ldlr^tm1Her
B6.129S7-Ldlr/J

cardiovascular system phenotype

atherosclerotic lesions
- after 8 or 20 weeks on a cholesterol diet aortic lesion size is increased compared to mice that are homozygous for both Ldlr^tm1Her and Ifng^tm1Ts

integument phenotype

alopecia
- when fed a high fat diet

scaly skin
- when fed a high fat diet

thick skin
- when fed a high fat diet

endocrine/exocrine gland phenotype

abnormal adrenal gland morphology
- when fed a high fat diet, mice exhibit an increase in cholesterol content in the adrenal gland

liver/biliary system phenotype

abnormal liver physiology
- LDL updake is decreased by about 2X

hepatic steatosis
- when fed a high fat diet, mice exhibit larger diameter and more frequent lipid droplets than in Apoa1^tm1Unc Ldlr^tm1Her homozygotes

increased liver cholesterol level
- when fed a high fat diet, mice exhibit a greater increase in liver cholesterol content (11-fold) compared to in similarly treated Apoa1^tm1Unc Ldlr^tm1Her homozygotes (2.5-fold)

mammalian phenotype

homeostasis/metabolism phenotype
- Normal - mice fed a Western diet exhibit normal HDL cholesterol

homeostasis/metabolism phenotype

decreased circulating triglyceride level
- when fed regular chow or a high fat diet for 16 weeks, serum triglyceride levels are decreased compared to similarly treated Apoa1^tm1Unc Ldlr^tm1Her homozygotes

increased cholesterol level
- when fed a high fat diet, mice exhibit an increase in cholesterol content in the adrenal gland

increased circulating cholesterol level
- 15 fold higher on a normal diet than controls
- 40 fold higher than controls on a high fat diet
- when fed a high fat diet, mice exhibit a greater increase in VLDL and LDL (6-fold) compared to Ldlr^tm1Her homozygotes (3-fold)
- whether are fed a high fat diet or regular chow, plasma cholesterol levels are increased relative to similarly treated Apoa1^tm1Unc Ldlr^tm1Her homozygotes

increased circulating HDL cholesterol level
- when fed regular chow or a high fat diet for 16 weeks, serum HDL levels are increased compared to similarly treated Apoa1^tm1Unc Ldlr^tm1Her homozygotes

increased circulating LDL cholesterol level
- when fed a high fat diet, mice exhibit a greater increase in VLDL and LDL (6-fold) compared to Ldlr^tm1Her homozygotes (3-fold)
- when fed a Western diet compared to Ldlr^tm1Her homozygotes fed regular chow

increased circulating triglyceride level
- when fed a Western diet

increased circulating VLDL cholesterol level
- when fed a high fat diet, mice exhibit a greater increase in VLDL and LDL (6-fold) compared to Ldlr^tm1Her homozygotes (3-fold)
- when fed a Western diet

increased liver cholesterol level
- when fed a high fat diet, mice exhibit a greater increase in liver cholesterol content (11-fold) compared to in similarly treated Apoa1^tm1Unc Ldlr^tm1Her homozygotes (2.5-fold)

Genotype: Ldlr^tm1Her/Ldlr⁺
involves: 129S7/SvEvBrd * C57BL/6 * DBA/2

homeostasis/metabolism phenotype

hyperglycemia
- streptozotocin (STZ) treatment leads to 3-fold higher level of blood glucose in mice fed a high fat diet
- these high glucose levels persist for at least 12 weeks after STZ treatment

Genotype: Ldlr^tm1Her/Ldlr^tm1Her
involves: 129P2/OlaHsd * 129S7/SvEvBrd * C57BL/6 * DBA

homeostasis/metabolism phenotype

abnormal cholesterol homeostasis
- increase in the APOB lipoprotein cholesterol level compared to wild-type controls
- plasma cholesterol is nearly equal distribution between the HDL and LDL fractions
- the ratio of saturated + monounsaturated/polyunsaturated cholesterol ester fatty acid species in the LDL fraction is significantly decreased compared to Apoe^tm1Unc single mutants
- there is a 2.3 fold decrease in the ratio of saturated + monounsaturated/polyunsaturated cholesterol ester fatty acid species compared to Apoe^tm1Unc single mutants
- ts

abnormal circulating protein level
- increase in APOB-100

abnormal lipid homeostasis
- the HDL phospholipid fraction contains less 16:0 and 18:0 species and is enriched for 20:4 and 22:6 species compared to Apoe^tm1Unc single mutants

Genotype: Ldlr^tm1Her/Ldlr^tm1Her
involves: 129S7/SvEvBrd * C57BL/6 * SJL

homeostasis/metabolism phenotype

increased circulating cholesterol level
- total cholesterol greatly elevated

increased circulating LDL cholesterol level
- greatly elevated

Genotype: Ldlr^tm1Her/Ldlr⁺
B6.129S7-Ldlr

homeostasis/metabolism phenotype

increased circulating cholesterol level
- seen at 3-4 months of age

increased circulating triglyceride level
- seen at 3-4 months of age

Genotype: Ldlr^tm1Her/Ldlr^tm1Her
involves: 129S7/SvEvBrd * C57BL/6J

cardiovascular system phenotype

atherosclerotic lesions
- males show more aortic atherosclerosis than females, both in the arch and in the thoracic and abdominal aorta, whereas the average plasma cholesterol levels are similar in males and females
- mice fed a cholate-free high-cholesterol diet (1%) for 6 months develop more extensive lesions throughout the aorta compared to controls which show smaller lesions that are almost exclusively in the aortic origin; the extent of atherosclerosis in the entire aorta correlates with the size of lesions in the aortic origin
- re aorta correlates with the size of lesions in the aortic origin

increased susceptibility to atherosclerosis
- when fed a high-cholesterol diet, mice develop more extensive atherosclerotic lesions than similarly fed controls, with males more affected than females

homeostasis/metabolism phenotype

increased circulating cholesterol level
- mice fed a high-fat diet (1% cholesterol) exhibit increased average total plasma cholesterol levels

References

Ishibashi S; Brown MS; Goldstein JL; Gerard RD; Hammer RE; Herz J. 1993. Hypercholesterolemia in low density lipoprotein receptor knockout mice and its reversal by adenovirus-mediated gene delivery [see comments] J Clin Invest 92(2):883-93PubMed: 8349823 MGI: J:37394

Additional - Ldlr^tm1Her related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Standard PCR:Ldlr-alternate 1
- Genotyping resources and troubleshooting
Breeding Considerations

When maintaining a live colony, homozygous mice may be bred together.
- Additional Breeding and Husbandry Support
Citation
When using the CByJ.129S7(B6)-Ldlr^tm1Her/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #012845 in your Materials and Methods section.

Animal Health Reports

Facility Barrier Level Descriptions

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

Pricing & Availability

Cryo Recovery

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Genotype

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	Heterozygous for Ldlr<tm1Her>

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Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Control Suggestions

Approximate Controls

Additional Information

Selected References

Ldlrtm1Her

Allele Symbol: Ldlrtm1Her

Disease Terms

Model with phenotypic similarity to human disease where etiologies involve orthologs. Human genes are associated with this disease. Orthologs of those genes appear in the mouse genotype(s).

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: Ldlrtm1Her related

Mammalian Phenotype Terms by Genotype

Genotype: Ldlrtm1Her/Ldlrtm1Herinvolves: 129S7/SvEvBrd * C57BL/6

behavior/neurological phenotype

cellular phenotype

growth/size/body region phenotype

hematopoietic system phenotype

homeostasis/metabolism phenotype

immune system phenotype

liver/biliary system phenotype

nervous system phenotype

pigmentation phenotype

vision/eye phenotype

cardiovascular system phenotype

Genotype: Ldlrtm1Her/Ldlrtm1Herinvolves: 129S7/SvEvBrd

cardiovascular system phenotype

homeostasis/metabolism phenotype

Genotype: Ldlrtm1Her/Ldlrtm1Herinvolves: 129S6/SvEvTac * 129S7/SvEvBrd * C57BL/6

cardiovascular system phenotype

homeostasis/metabolism phenotype

Genotype: Ldlrtm1Her/Ldlrtm1HerB6.129S7-Ldlr

adipose tissue phenotype

growth/size/body region phenotype

hematopoietic system phenotype

homeostasis/metabolism phenotype

behavior/neurological phenotype

immune system phenotype

liver/biliary system phenotype

nervous system phenotype

cardiovascular system phenotype

Genotype: Ldlrtm1Her/Ldlrtm1HerB6.129S7-Ldlr/J

cardiovascular system phenotype

integument phenotype

endocrine/exocrine gland phenotype

liver/biliary system phenotype

mammalian phenotype

homeostasis/metabolism phenotype

Genotype: Ldlrtm1Her/Ldlr+involves: 129S7/SvEvBrd * C57BL/6 * DBA/2

homeostasis/metabolism phenotype

Genotype: Ldlrtm1Her/Ldlrtm1Herinvolves: 129P2/OlaHsd * 129S7/SvEvBrd * C57BL/6 * DBA

homeostasis/metabolism phenotype

Genotype: Ldlrtm1Her/Ldlrtm1Herinvolves: 129S7/SvEvBrd * C57BL/6 * SJL

homeostasis/metabolism phenotype

Genotype: Ldlrtm1Her/Ldlr+B6.129S7-Ldlr

homeostasis/metabolism phenotype

Genotype: Ldlrtm1Her/Ldlrtm1Herinvolves: 129S7/SvEvBrd * C57BL/6J

cardiovascular system phenotype

homeostasis/metabolism phenotype

References

Additional - Ldlrtm1Her related

Genotyping Protocols

Breeding Considerations

Citation

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

Live Mouse

Cryorecovery - Pricing

Related Products and Services

Payment Terms and Conditions

The Jackson Laboratory's Genotype Promise

Terms Of Use

Additional Use Restrictions Apply

Licensing Information

Ldlr^tm1Her

Allele Symbol: Ldlr^tm1Her

Genotype: Ldlr^tm1Her related

Genotype: Ldlr^tm1Her/Ldlr^tm1Her
involves: 129S7/SvEvBrd * C57BL/6

Genotype: Ldlr^tm1Her/Ldlr^tm1Her
involves: 129S7/SvEvBrd

Genotype: Ldlr^tm1Her/Ldlr^tm1Her
involves: 129S6/SvEvTac * 129S7/SvEvBrd * C57BL/6

Genotype: Ldlr^tm1Her/Ldlr^tm1Her
B6.129S7-Ldlr

Genotype: Ldlr^tm1Her/Ldlr^tm1Her
B6.129S7-Ldlr/J

Genotype: Ldlr^tm1Her/Ldlr⁺
involves: 129S7/SvEvBrd * C57BL/6 * DBA/2

Genotype: Ldlr^tm1Her/Ldlr^tm1Her
involves: 129P2/OlaHsd * 129S7/SvEvBrd * C57BL/6 * DBA

Genotype: Ldlr^tm1Her/Ldlr^tm1Her
involves: 129S7/SvEvBrd * C57BL/6 * SJL

Genotype: Ldlr^tm1Her/Ldlr⁺
B6.129S7-Ldlr

Genotype: Ldlr^tm1Her/Ldlr^tm1Her
involves: 129S7/SvEvBrd * C57BL/6J

Additional - Ldlr^tm1Her related