Overview

Also Known As:Ldlr KO

Mice homozygous for the Ldlr^tm1Her mutation have an elevated serum cholesterol level of 200-400 mg/dl and they have very high levels (>2,000 mg/dl) when fed a high fat diet. Normal serum cholesterol in the mouse is 80-100 mg/dl.

Donating Investigator

IMR Colony, The Jackson Laboratory

Genetic overview

Genetic Background	Generation
000664 C57BL/6J

Ldlr^tm1Her

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

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Research Applications

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

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Base Price

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$133.35 Domestic price for male 3-week

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Details

Detailed Description

Mice homozygous for the Ldlr^tm1Her mutation have an elevated serum cholesterol level of 200-400 mg/dl and they have very high levels (>2,000 mg/dl) when fed a high fat diet. Normal serum cholesterol in the mouse is 80-100 mg/dl.

Development

The Ldlr^tm1Her mutant strain was developed in the laboratory of Dr. Robert Hammer and Dr. Joachim Herz at the Howard Hughes Medical Institute Research Laboratories, University of Texas Southwestern Medical Center at Dallas. Insertion of a neomycin resistance cassette into exon 4 is predicted to encode a truncated non-functional protein that will not bind LDL, and that lacks a membrane spanning segment. The 129-derived AB1 ES cell line was used. The strain has been backcrossed to C57BL/6J mice for 10 generations (N10).

Control Suggestions

000664 C57BL/6J

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

View All References

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:

Diabetes and Obesity Research
- Obesity With Diabetes
  - diet-induced

Genotype: Ldlr^tm1Her related

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

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⁺
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^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

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

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⁺
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

Phenotype Information

Body Weight Information - JAX^® Mice Strain - B6.129S7-Ldlr^tm1Her/J (002207)
Cardiovascular Disease Phenotypes

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 References

Babaev VR; Patel MB; Semenkovich CF; Fazio S; Linton MF. 2000. Macrophage lipoprotein lipase promotes foam cell formation and atherosclerosis in low density lipoprotein receptor-deficient mice J Biol Chem 275(34):26293-9PubMed: 10858435 MGI: J:64000
Binder CJ; Horkko S; Dewan A; Chang MK; Kieu EP; Goodyear CS; Shaw PX; Palinski W; Witztum JL; Silverman GJ. 2003. Pneumococcal vaccination decreases atherosclerotic lesion formation: molecular mimicry between Streptococcus pneumoniae and oxidized LDL. Nat Med 9(6):736-43PubMed: 12740573 MGI: J:83726
Freemerman AJ; Zhao L; Pingili AK; Teng B; Cozzo AJ; Fuller AM; Johnson AR; Milner JJ; Lim MF; Galanko JA; Beck MA; Bear JE; Rotty JD; Bezavada L; Smallwood HS; Puchowicz MA; Liu J; Locasale JW; Lee DP; Bennett BJ; Abel ED; Rathmell JC; Makowski L. 2019. Myeloid Slc2a1-Deficient Murine Model Revealed Macrophage Activation and Metabolic Phenotype Are Fueled by GLUT1. J Immunol 202(4):1265-1286PubMed: 30659108 MGI: J:272884
Herz J; Qiu SQ; Oesterle A; DeSilva HV; Shafi S; Havel RJ. 1995. Initial hepatic removal of chylomicron remnants is unaffected but endocytosis is delayed in mice lacking the low density lipoprotein receptor. Proc Natl Acad Sci U S A 92(10):4611-5PubMed: 7753850 MGI: J:25195
Huszar D; Varban ML; Rinninger F; Feeley R; Arai T; Fairchild-Huntress V; Donovan MJ; Tall AR. 2000. Increased LDL cholesterol and atherosclerosis in LDL receptor-deficient mice with attenuated expression of scavenger receptor B1. Arterioscler Thromb Vasc Biol 20(4):1068-73PubMed: 10764675 MGI: J:62371
Ishibashi S; Goldstein JL; Brown MS; Herz J; Burns DK. 1994. Massive xanthomatosis and atherosclerosis in cholesterol-fed low density lipoprotein receptor-negative mice. J Clin Invest 93(5):1885-93PubMed: 8182121 MGI: J:77012
Ishibashi S; Herz J; Maeda N; Goldstein JL; Brown MS. 1994. The two-receptor model of lipoprotein clearance: tests of the hypothesis in knockout mice lacking the low density lipoprotein receptor, apolipoprotein E, or both proteins. Proc Natl Acad Sci U S A 91(10):4431-5PubMed: 8183926 MGI: J:18138
Jahrling JB; Lin AL; DeRosa N; Hussong SA; Van Skike CE; Girotti M; Javors M; Zhao Q; Maslin LA; Asmis R; Galvan V. 2018. mTOR drives cerebral blood flow and memory deficits in LDLR(-/-) mice modeling atherosclerosis and vascular cognitive impairment. J Cereb Blood Flow Metab 38(1):58-74PubMed: 28511572 MGI: J:271732
Keren P; George J; Shaish A; Levkovitz H; Janakovic Z; Afek A; Goldberg I; Kopolovic J; Keren G; Harats D. 2000. Effect of hyperglycemia and hyperlipidemia on atherosclerosis in LDL receptor-deficient mice: establishment of a combined model and association with heat shock protein 65 immunity. Diabetes 49(6):1064-9PubMed: 10866061 MGI: J:62295
Knouff C; Briand O; Lestavel S; Clavey V; Altenburg M; Maeda N. 2004. Defective VLDL metabolism and severe atherosclerosis in mice expressing human apolipoprotein E isoforms but lacking the LDL receptor. Biochim Biophys Acta 1684(1-3):8-17PubMed: 15450205 MGI: J:92554
Kulinski A; Rustaeus S; Vance JE. 2002. Microsomal Triacylglycerol Transfer Protein Is Required for Lumenal Accretion of Triacylglycerol Not Associated with ApoB, as Well as for ApoB Lipidation. J Biol Chem 277(35):31516-25PubMed: 12072432 MGI: J:78774
Lie J; de Crom R; van Gent T; van Haperen R; Scheek L; Sadeghi-Niaraki F; van Tol A. 2004. Elevation of plasma phospholipid transfer protein increases the risk of atherosclerosis despite lower apolipoprotein B-containing lipoproteins. J Lipid Res 45(5):805-11PubMed: 14993244 MGI: J:89308
Merkel M; Velez-Carrasco W; Hudgins LC; Breslow JL. 2001. Compared with saturated fatty acids, dietary monounsaturated fatty acids and carbohydrates increase atherosclerosis and VLDL cholesterol levels in LDL receptor-deficient, but not apolipoprotein E-deficient, mice. Proc Natl Acad Sci U S A 98(23):13294-9PubMed: 11606787 MGI: J:72580
Nicolaou A; Northoff BH; Sass K; Ernst J; Kohlmaier A; Krohn K; Wolfrum C; Teupser D; Holdt LM. 2017. Quantitative trait locus mapping in mice identifies phospholipase Pla2g12a as novel atherosclerosis modifier. Atherosclerosis 265:197-206PubMed: 28917158 MGI: J:290574
Qing H; Jones KL; Heywood EB; Lu H; Daugherty A; Bruemmer D. 2017. Deletion of the NR4A nuclear receptor NOR1 in hematopoietic stem cells reduces inflammation but not abdominal aortic aneurysm formation. BMC Cardiovasc Disord 17(1):271PubMed: 29047330 MGI: J:271770
Renard CB; Kramer F; Johansson F; Lamharzi N; Tannock LR; von Herrath MG; Chait A; Bornfeldt KE. 2004. Diabetes and diabetes-associated lipid abnormalities have distinct effects on initiation and progression of atherosclerotic lesions. J Clin Invest 114(5):659-68PubMed: 15343384 MGI: J:92597
Schiller NK; Black AS; Bradshaw GP; Bonnet DJ; Curtiss LK. 2004. Participation of macrophages in atherosclerotic lesion morphology in LDLr-/- mice. J Lipid Res 45(8):1398-409PubMed: 15175354 MGI: J:91367
Schonbeck U; Sukhova GK; Shimizu K; Mach F; Libby P. 2000. Inhibition of CD40 signaling limits evolution of established atherosclerosis in mice [see comments] Proc Natl Acad Sci U S A 97(13):7458-63PubMed: 10861012 MGI: J:63076
Schreyer SA; Vick C; Lystig TC; Mystkowski P; LeBoeuf RC. 2002. LDL receptor but not apolipoprotein E deficiency increases diet-induced obesity and diabetes in mice. Am J Physiol Endocrinol Metab 282(1):E207-14PubMed: 11739102 MGI: J:75609
Schreyer SA; Vick CM; LeBoeuf RC. 2002. Loss of Lymphotoxin-alpha but Not Tumor Necrosis Factor-alpha Reduces Atherosclerosis in Mice. J Biol Chem 277(14):12364-8PubMed: 11809756 MGI: J:75788
Shi W; Wang X; Wong J; Hedrick CC; Wong H; Castellani LW; Lusis AJ. 2004. Effect of macrophage-derived apolipoprotein E on hyperlipidemia and atherosclerosis of LDLR-deficient mice. Biochem Biophys Res Commun 317(1):223-9PubMed: 15047172 MGI: J:88891
Tangirala RK; Pratico D; FitzGerald GA; Chun S; Tsukamoto K; Maugeais C; Usher DC; Pure E; Rader DJ. 2001. Reduction of isoprostanes and regression of advanced atherosclerosis by apolipoprotein E. J Biol Chem 276(1):261-6PubMed: 11024044 MGI: J:66833
Truong TQ; Auger A; Denizeau F; Brissette L. 2000. Analysis of low-density lipoprotein catabolism by primary cultures of hepatic cells from normal and low-density lipoprotein receptor knockout mice. Biochim Biophys Acta 1484(2-3):307-15PubMed: 10760479 MGI: J:61821
Tumurkhuu G; Dagvadorj J; Porritt RA; Crother TR; Shimada K; Tarling EJ; Erbay E; Arditi M; Chen S. 2018. Chlamydia pneumoniae Hijacks a Host Autoregulatory IL-1beta Loop to Drive Foam Cell Formation and Accelerate Atherosclerosis. Cell Metab 28(3):432-448.e4PubMed: 29937375 MGI: J:266038
van Eck M; Bos IS; Kaminski WE; Orso E; Rothe G; Twisk J; Bottcher A; Van Amersfoort ES; Christiansen-Weber TA; Fung-Leung WP; Van Berkel TJ; Schmitz G. 2002. Leukocyte ABCA1 controls susceptibility to atherosclerosis and macrophage recruitment into tissues. Proc Natl Acad Sci U S A 99(9):6298-303PubMed: 11972062 MGI: J:76337
Wang Y; Wang W; Wang N; Tall AR; Tabas I. 2017. Mitochondrial Oxidative Stress Promotes Atherosclerosis and Neutrophil Extracellular Traps in Aged Mice. Arterioscler Thromb Vasc Biol 37(8):e99-e107PubMed: 28596373 MGI: J:268720
Welch CL; Bretschger S; Latib N; Bezouevski M; Guo Y; Pleskac N; Liang CP; Barlow C; Dansky H; Breslow JL; Tall AR. 2001. Localization of atherosclerosis susceptibility loci to chromosomes 4 and 6 using the Ldlr knockout mouse model. Proc Natl Acad Sci U S A 98(14):7946-51PubMed: 11438740 MGI: J:70259
Welch CL; Bretschger S; Wen PZ; Mehrabian M; Latib N; Fruchart-Najib J; Fruchart JC; Myrick C; Lusis AJ. 2004. Novel QTLs for HDL levels identified in mice by controlling for Apoa2 allelic effects: confirmation of a chromosome 6 locus in a congenic strain. Physiol Genomics 17(1):48-59PubMed: 14722362 MGI: J:88731
Whitman SC; Rateri DL; Szilvassy SJ; Cornicelli JA; Daugherty A. 2002. Macrophage-specific expression of class A scavenger receptors in LDL receptor(-/-) mice decreases atherosclerosis and changes spleen morphology. J Lipid Res 43(8):1201-8PubMed: 12177164 MGI: J:78922

Additional - Ldlr^tm1Her related

Technical Support

CONTACT TECHNICAL SUPPORT

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

This strain is a good breeder.

This Ldlr^tm1Her strain is maintained by mating homozygous siblings. Only homozygous mice may be ordered.
- Additional Breeding and Husbandry Support
Mating System
- Homozygote x Homozygote
Appearance
- black
  Related Genotype: a/a
Citation
When using the Ldlr KO mouse strain in a publication, please cite the originating article(s) and include JAX stock #002207 in your Materials and Methods section.

Animal Health Reports

Facility Barrier Level Descriptions

RB10 (Maximum)

AX4 (Standard)

Pricing & Availability

Readily Available

Domestic
International

Live Mouse

Age

Genotype

Price

weeks

Cryorecovery - Pricing

Service/Product	Description	Price
	Homozygous for Ldlr<tm1Her>

Payment Terms and Conditions

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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.

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General Terms and Conditions

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JAX® Mice, Products & Services Conditions of Use

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Also Known As:Ldlr KO

Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Control Suggestions

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

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+B6.129S7-Ldlr

homeostasis/metabolism phenotype

Phenotype Information

References

Additional References

Additional - Ldlrtm1Her related

Genotyping Protocols

Breeding Considerations

Mating System

Appearance

Citation

Animal Health Reports

Live Mouse

Cryorecovery - Pricing

Payment Terms and Conditions

The Jackson Laboratory's Genotype Promise

Terms Of Use

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

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

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

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

Additional - Ldlr^tm1Her related