Overview

Also Known As:ApoE KO

Mice homozygous for the Apoe^tm1Unc knock-out mutation show a marked increase in total plasma cholesterol levels that are unaffected by age or gender. Fatty streaks in the proximal aorta are found at three months of age. The lesions increase with age and progress to lesions with less lipid but more elongated cells, typical of a more advanced stage of pre-atherosclerotic lesion. These ApoE KO mice are useful for studying cardiovascular disease, atherosclerosis and fat metabolism, as well as the role of ApoE in Alzheimer's disease.

Donating Investigator

Dr. Nobuyo Maeda, University of North Carolina at Chapel Hill

Genetic overview

Genetic Background	Generation
	Contact Technical Support (2018-07-27 00:00:00)

Apoe^tm1Unc

Allele Type	Gene Symbol	Gene Name
Targeted (Null/Knockout)	Apoe	apolipoprotein E

View Genetics

Research Applications

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

View All Research Applications

Base Price

Starting at:

$115.98 Domestic price for female 4-week

View Price List

Details

Detailed Description

Mice homozygous for the Apoe^tm1Unc mutation show a marked increase in total plasma cholesterol levels that are unaffected by age or sex. Fatty streaks in the proximal aorta are found at 3 months of age. The lesions increase with age and progress to lesions with less lipid but more elongated cells, typical of a more advanced stage of pre-atherosclerotic lesion. Moderately increased triglyceride levels have been reported in mice with this mutation on a mixed C57BL/6 x 129 genetic background. Aged apoE-deficient mice (>17 months) have been shown to develop xanthomatous lesions in the brain consisting mostly of crystalline cholesterol clefts, lipid globules, and foam cells. Smaller xanthomas were seen in the choroid plexus and ventral fornix. Additional studies indicate that apoE-deficient mice have altered responses to stress, impaired spatial learning and memory, altered long term potentiation, and synaptic damage.

Development

The Apoe^tm1Unc mutant strain was developed in the laboratory of Dr. Nobuyo Maeda at The University of North Carolina at Chapel Hill. The 129P2/OlaHsd-derived E14Tg2a ES cell line was used. The plasmid used is designated as pNMC109 and the founder line is T-89 in the primary reference. This C57BL/6J-congenic Apoe^tm1Unc strain was produced by backcrossing at least 10 generations to C57BL/6J inbred mice. These mice have black coat color.

Of note, previous to 1995, mice backcrossed 6 times (N6) to C57BL/6J mice were distributed solely. Mice from the N6 generation were homozygous for pink-eyed dilution p giving them pink eyes and a silver coat color. The E14Tg2a ES cell line carried this recessive mutation which remained linked to the targeted Apoe gene on Chromosome 7 at the N6 backcross generation. Mice from the N6 colony are no longer available for distribution [1995].

Control Suggestions

000664 C57BL/6J

Additional Information

Considerations for Choosing Controls

Selected References

Piedrahita JA; Zhang SH; Hagaman JR; Oliver PM; Maeda N. 1992. Generation of mice carrying a mutant apolipoprotein E gene inactivated by gene targeting in embryonic stem cells. Proc Natl Acad Sci U S A 89(10):4471-5PubMed: 1584779 MGI: J:1050

View All References

Genetics

Apoe^tm1Unc

Allele Symbol: Apoe^tm1Unc

Allele Name	targeted mutation 1, University of North Carolina
Allele Type	Targeted (Null/Knockout)
Allele Synonym(s)	AopE(-); apoE-; APOE KO; Apoe^tm1Un; apoE0; ApoE-KO; EKO; epsilon-; mE^-; mEKO
Gene Symbol and Name	Apoe, apolipoprotein E
Gene Synonym(s)
Strain of Origin	129P2/OlaHsd
Chromosome	7
Molecular Note	Insertion of a neomycin resistance cassette deleted part of exon 3 and part of intron 3 of the Apoe gene. Plasma from homozygous mutant mice gave no detectable immunoprecipitate by the Ouchterlony double immunodiffusion test using a rabbit antibody to rat APOE.
Mutations Made By	Dr. Nobuyo Maeda, University of North Carolina at Chapel Hill

Disease/Phenotype

Disease Terms

Research Areas By Phenotype

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

Neurobiology Research
- Behavioral and Learning Defects
- Neurodegeneration
- Alzheimer's Disease
  - APOE mutants
Diabetes and Obesity Research
- Obesity Without Diabetes
  - diet-induced
Cardiovascular Research
- Hypertriglyceridemia
- Diet-Induced Atherosclerosis
- Vascular Defects
- Heart Abnormalities
- Hypercholesterolemia
- Other
  - altered lipoprotein profile
  - altered fat metabolism
Research Tools
- Cardiovascular Research
- Metabolism Research
- Neurobiology Research
Metabolism Research
- Lipid Metabolism

Genotype: Apoe^tm1Unc related

Mouse/Human Gene Homologs
- hyperlipoproteinemia, type III
- Alzheimer's
Cardiovascular Research
- Atherosclerosis
- 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: Apoe^tm1Unc/Apoe^tm1Unc
involves: 129P2/OlaHsd

muscle phenotype

decreased vasodilation
- impaired vasodilation induced by sodium nitroprusside 7 days after partial ligation of the left common carotid

nervous system phenotype

decreased cerebral infarct size
- compared to in Tg(Eno2-APP751)10Cord Apoe^tm1Unc/Apoe^tm1Unc mice

abnormal dendrite morphology
- mutants have lower levels of MAP 2-positive neuronal dendrites than wild-type; at 3 months, levels are similar in mutants and controls

behavior/neurological phenotype

increased anxiety-related response
- in the elevated-plus maze, mice show increased anxiety with reduced time and distance moved in the open arms; mice have significantly lower number of open-arm entries than wild-type
- effect is age-dependent; phenotype is present in older mice, but not in young 2-4 month-old mice

increased startle reflex
- response is higher in mice at 6 months of age compared to wild-type

cardiovascular system phenotype

abnormal susceptibility to atherosclerosis
- atherosclerotic lesion development is well advanced by 4-6 weeks after partial ligation of the left common carotid
- atherosclerotic lesions begin to form in the left common carotid by 2 weeks after partial ligation of the left common carotid

decreased vasodilation
- impaired vasodilation induced by sodium nitroprusside 7 days after partial ligation of the left common carotid

increased susceptibility to atherosclerosis
- bone marrow transplanted into Apoa1^tm1Unc homozygotes confer 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

increased circulating corticosterone level
- all males have higher plasma concentrations than wild-type after behavioral testing

decreased cerebral infarct size
- compared to in Tg(Eno2-APP751)10Cord Apoe^tm1Unc/Apoe^tm1Unc mice

increased circulating cholesterol level
- when fed a chow or Western-type diet for 2 weeks, mice exhibit increased serum cholesterol compared with Apobec1^tm1Chan homozygotes and wild-type mice

Genotype: Apoe^tm1Unc/Apoe^tm1Unc
involves: 129P2/OlaHsd * C57BL/6 * DBA

homeostasis/metabolism phenotype

abnormal cholesterol homeostasis
- increase in the APOB lipoprotein cholesterol level compared to wild-type controls
- there is a 2.3 fold increase in the ratio of saturated + monounsaturated/polyunsaturated cholesterol ester fatty acid species compared to Ldlr^tm1Her single mutants
- ts
- the ratio of saturated + monounsaturated/polyunsaturated cholesterol ester fatty acid species in the LDL fraction is significantly increased compared to Ldlr^tm1Her single mutants

decreased circulating HDL cholesterol level
- about a 50% decrease in HDL compared to controls

increased circulating cholesterol level
- increased total cholesterol and esterfied cholesterol levels in the plasma

increased circulating phospholipid level

abnormal lipid homeostasis
- the HDL phospholipid fraction is enriched in 16:0 and 18:0 species and contains less 20:4 and 22:6 species compared to Ldlr^tm1Her single mutants

abnormal circulating protein level
- increase in APOB-48

Genotype: Apoe^tm1Unc/Apoe^tm1Unc
involves: 129P2/OlaHsd * C57BL/6

homeostasis/metabolism phenotype

increased circulating cholesterol level
- relative to wild-type
- total cholesterol levels are about 4-fold higher than controls with a mean of 379 mg/dl
- mean total cholesterol levels are elevated about 5-fold over wild-type to 434 mg/dl
- plasma cholesterol levels increase significantly with time

increased circulating triglyceride level
- relative to wild-type
- circulating triglyceride levels are 123 mg/dl compared to 73 mg/dl in controls

decreased circulating HDL cholesterol level
- mean HDL levels (33 mg/dl) are 45% of that found in controls

increased circulating LDL cholesterol level
- mice have elevated levels of LDL in the blood

hyperlipidemia
- relative to wild-type

increased circulating VLDL cholesterol level
- the majority of lipoprotein particles in the blood are in the VLDL size range
- very high levels of VLDL cholesterol

increased prostaglandin level
- PGE2 level doubles on a high fat diet
- amount of PGE2 in aortas is 4X higher than in controls

immune system phenotype

lung inflammation
- isolated small foci of mononuclear cells are present in lung after 6 weeks of high-fat feeding

nervous system phenotype

abnormal astrocyte physiology
- astrocytes secrete less phospholipids or free cholesterol compared to wild-type astrocytes

abnormal synapse morphology
- elevated cholesterol in the exofacial leaflet of the synaptic plasma membrane but not so high as for Ldlr deficient mice
- cholesterol levels in the cytofacial leaflet are reduced

respiratory system phenotype

lung inflammation
- isolated small foci of mononuclear cells are present in lung after 6 weeks of high-fat feeding

cardiovascular system phenotype

atherosclerotic lesions
- fatty streaks with foam cells are found in the proximal aorta of 3-8 month old mice fed normal chow
- lesions get bigger with age and near total occlusion at the entrance of a coronary artery can be observed at 8 months of age
- mice exhibit atherosclerotic lesions in the aorta and aortic root
- extent of atherosclerosis correlates with plasma cholesterol levels
- aortic cartilaginous metaplasia is noted in the most severely affected mice
- greater than in wild-type
- 75% of mice develop lesions in the aortic arch with most females and some males having calcification within the lesions
- the foam cells are often adjacent to valve attachment sites and can form multi-layers

Genotype: Apoe^tm1Unc/Apoe^tm1Unc
involves: 129P2/OlaHsd * C57BL/6 * FVB/N

cardiovascular system phenotype

atherosclerotic lesions
- lesions are observed in aortas of nontransgenic mice

Genotype: Apoe^tm1Unc/Apoe^tm1Unc
involves: 129P2/OlaHsd * 129S4/SvJae * C57BL/6

cardiovascular system phenotype

atherosclerotic lesions
- most severe in the aortic arch region

Genotype: Apoe^tm1Unc/Apoe⁺
involves: 129P2/OlaHsd * C57BL/6

homeostasis/metabolism phenotype

increased circulating triglyceride level
- circulating triglyceride levels are 39% higher than in wild-type controls

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

Genotype: Apoe^tm1Unc/Apoe^tm1Unc
B6.129P2-Apoe/J

behavior/neurological phenotype

abnormal spatial learning
- longer latency to find the platform in Morris maze tests
- slow to acquire a preference for the target quadrant and the magnitude of the preference is always less than controls

increased thigmotaxis
- elevated thigmotaxis in Morris maze tests

homeostasis/metabolism phenotype

increased circulating cholesterol level
- on an atherosclerotic diet, homozygotes show a further significant increase in plasma TC levels relative to homozygotes on a normal diet
- 5 fold increase in total cholesterol at 24 and 36 weeks
- increasing with age; 4-fold increase in plasma total cholesterol levels in 10-12 week old mutants and 13-fold increase at 29 weeks
- significantly increased relative to wild-type controls at 24 weeks of age; levels in mutants after induction of chronic graft versus host disease (cGVH) to induce systemic lupus erythematosus (SLE) are equivalent to the Apoe-null mice
- total serum cholesterol 20 fold higher than controls on high fat diet where controls show 4 fold increase over normal diet
- on a normal diet, homozygotes display significantly increased plasma total cholesterol (TC) levels relative to C57BL/6J control mice
- total serum cholesterol 70 fold higher than controls on a normal diet
- exercise (15 or 60 min/day swim) causes no significant changes in total cholesterol levels among homozygotes or wild-type mice relative to sedentary, genotype-matched controls

abnormal glomerular capillary thrombosis
- lipid droplets filling glomerular capillary lumina at 36 weeks in about 50% of mice
- such thrombus-like structures commonly dsiplay a laminated appearance with adjacent foam cells in the mesangium

abnormal circulating cholesterol level
- decreased HDL/total cholesterol ratio
- decreased HDL/LDL ratio

decreased circulating HDL cholesterol level

increased cholesterol efflux
- in perhexiline-treated mice fed a high-fat diet

decreased circulating homocysteine level
- decrease in plasma total homocysteine levels

abnormal enzyme/coenzyme activity
- activity of cholesterol synthesis enzyme HMG-CoA reductase is reduced up to 60% in aging mice compared to 30% in wild-type aging mice

hyperlipidemia
- homozygotes develop hyperlipidemia; however, HDL cholesterol levels, body weight and blood glucose remain unchanged relative to C57BL/6J control mice on a normal diet, with no further differences noted on an atheroscletoric diet

decreased circulating glucose level

increased circulating triglyceride level
- on a normal diet, homozygotes display significantly increased plasma triglyceride levels relative to C57BL/6J control mice
- on an atherosclerotic diet, homozygotes show a further significant increase in plasma triglyceride levels relative to homozygotes on a normal diet
- 2-fold increase in plasma triglyceride levels in 10-12 week old mutants

xanthoma
- 1 of 11 aged mice on a normal diet develops cerebral xanthoma
- eruptive xanthomas on shoulder and back areas with lipids and extracellular matix as the predominant components

increased circulating VLDL cholesterol level
- on an atherosclerotic diet, homozygotes show a further significant increase in plasma VLDL cholesterol levels relative to homozygotes on a normal diet
- on a normal diet, homozygotes display significantly increased plasma VLDL cholesterol levels relative to C57BL/6J control mice

decreased circulating triglyceride level

increased circulating HDL cholesterol level
- in perhexiline-treated mice fed a high-fat diet

increased circulating LDL cholesterol level
- on a normal diet, homozygotes display significantly increased plasma LDL cholesterol levels relative to C57BL/6J control mice
- on an atherosclerotic diet, homozygotes show a further significant increase in plasma LDL levels relative to homozygotes on a normal diet

immune system phenotype

abnormal B cell activation
- spleen cells display polyclonal B cell activation, with increased expression of MHC II, Fas, and CD86 and lower expression of CD21, CD22, and CD23

abnormal CD4-positive, alpha beta T cell number
- ratio of Th2 to Th1 cells is increased from 4.4 to 11.4 on a normal diet and up to 20.9 on a high cholesterol diet
- clusters of CD4+ cells found in fatty streak lesions

decreased interferon-gamma secretion
- production is reduced when fed a high cholesterol diet

increased marginal zone B cell number
- increased 2-fold compared to wild-type

abnormal immune system morphology

increased spleen weight
- increased spleen weight while the thymus weight remains normal

increased susceptibility to systemic lupus erythematosus

decreased marginal zone B cell number
- with induction of SLE by cGVH, levels are slightly decreased compared to wild-type

increased immunoglobulin level
- mutants with cGVH-induced SLE show greatly increased levels compared to wild-type controls or untreated mutants

increased B cell number
- newly formed B cells are significantly increased compared to wild-type

abnormal T cell number
- increased numbers of cytokine producing T cells

blood vessel inflammation
- aortae show macrophage and T cell extravasation within atherosclerotic lesions

increased IgM level
- IgM response to tetanus toxoid is significantly increased as compared to controls

increased T-helper 2 cell number

abnormal immune system physiology

decreased susceptibility to type IV hypersensitivity reaction
- decreased antigen specific delayed hypersensitivity response

increased anti-nuclear antigen antibody level
- after induction of cGVH-SLE, mice display greatly increased levels of anti-chromatin antibodies compared to wild-type controls or non-cGVH mutants

abnormal immune serum protein physiology

decreased follicular B cell number
- decreased relative to controls

increased anti-double stranded DNA antibody level
- after induction of cGVH-SLE, mice display greatly increased levels compared to wild-type controls or non-cGVH-SLE mutants

increased autoantibody level
- after induction of cGVH-SLE, IgG and IgM anti-oxidized LDL and anti-cardiolipin antibodies are increased compared to wild-type or Apoe-null controls

integument phenotype

skin lesions
- progressive skin lesions, mainly seen as eruptive xanthomas on shoulder and back areas with lipids and extracellular matix as the predominant components

liver/biliary system phenotype

abnormal liver physiology
- hepatic uptake of LDL is increased two fold
- no significant change in serum alanine transaminase with high fat diet as is seen in controls (marker for liver damage)

mortality/aging

premature death
- 35% dead by 18 months

muscle phenotype

decreased vasodilation
- homozygotes fed a normal or atherosclerotic diet show severely impaired endothelium-dependent relaxation to acetylcholine in aortic rings relative to age-matched C57BL/6J control mice

impaired muscle relaxation
- relaxation response to acetylcholine in blood vessels is significantly attenuated at 13 months of age
- maximal response to acetylcholine is considerably reduced

nervous system phenotype

cochlear ganglion degeneration
- loss of ganglion cells is excerbated by an atherosclerotic diet
- at 24 weeks, homozygotes fed a normal diet show a reduced number of spiral ganglion cells in the basal turn of the cochlea

cochlear outer hair cell degeneration
- at 24 weeks, homozygotes fed a normal diet show almost complete loss of OHCs in the basal turn and some OHC loss in the middle turn
- OHC loss at the base turn is exacerbated by an atherosclerotic diet

abnormal blood-brain barrier function
- impaired blood-brain barrier and blood-nerve barrier as indicated by extensive extravasation of serum proteins into sciatic nerve, spinal cord and cerebellum and occasional extravasation into cortex and subcortex

cochlear inner hair cell degeneration
- at 24 weeks, homozygotes fed a normal diet show almost complete loss of IHCs in the basal turn and some IHC loss in the middle turn
- IHC loss at the base turn is exacerbated by an atherosclerotic diet

renal/urinary system phenotype

renal glomerulus lipidosis
- lipid droplets filling glomerular capillary lumina at 36 weeks in about 50% of mice
- glomerular foam cells in the mesangium, capillary lumina and within the glomerular stalk close to the vascular pole
- lipid deposits in arteriolar walls in the vascular poles

expanded mesangial matrix
- progressive increase in glomerular matrix, already evident at 24 weeks, associated with accumulation of laminin and collagen IV

abnormal kidney arterial blood vessel morphology
- arterioles of the vascular pole show a "foamy" degeneration of smooth muscle cells

dilated glomerular capillary
- at times mesangiolysis is associated with ballooning dilatation ("microaneurysm") of adjacent glomerular capillaries

kidney microaneurysm
- at times mesangiolysis is associated with ballooning dilatation ("microaneurysm") of adjacent glomerular capillaries

abnormal renal glomerulus morphology
- glomerular cell numbers are increased
- increased glomerular tuft area

mesangiolysis
- loss of mesangial matrix sometimes at 36 weeks but never at 24 weeks or in controls

respiratory system phenotype

abnormal lung hysteresivity
- percent increase in hysteresivity with age greater than in controls

abnormal pulmonary alveolus morphology
- fewer but larger alveoli at 3 months of age
- less surface area to volume

increased airway resistance
- resistance to airflow greater than controls at 3 months but not at 8 months of age

abnormal lung volume
- lung volume similar to controls at 3 months but 2.5 fold greater at 8 months of age

increased lung compliance
- dynamic and static compliance greater than controls at 8 months of age

skeleton phenotype

abnormal osteoblast physiology
- increased rate of bone formation

abnormal bone structure

increased compact bone thickness
- in vertebral bodies and tibia

increased bone mineral density
- higher bone mineralization density in vertebral bodies
- increased bone volume to tissue volume ratio

abnormal skeleton physiology

increased bone trabecula number
- increased number of trabeculae

taste/olfaction phenotype

impaired olfaction
- latency to taste vanillin-cued quinine significantly increased only at day 5
- slower than control to find buried food pellet although found pellets visually more rapidly
- preference for plain water over 0.1% iso-amyl alcohol moderate compared to the strong preference shown by controls

vision/eye phenotype

abnormal eye electrophysiology
- implicit times increased for a and b waves of dark adapted electroretinogram
- wave amplitudes attenuated for a and b waves of dark adapted electroretinogram

thin retinal inner nuclear layer
- cell numbers reduced

abnormal retinal inner nuclear layer morphology
- perinuclear vacuolation on a high cholesterol diet

thin retinal outer nuclear layer
- cell numbers reduced

cardiovascular system phenotype

abnormal aorta wall morphology
- endothelial nitric oxide synthase (eNOS) in mutant aortic wall is distinctly reduced
- Cx43 distribution at cell-cell junction shows significant disruption

abnormal blood flow velocity
- in addition, anesthetized homozygotes show significantly increased transmitral blood velocities relative to wild-type mice with peak mitral velocities at 92 ¿ 7.2 cm/s vs 47.2 ¿ 5.3 cm/s, and mean mitral velocities at 20.6 ¿ 1.7 vs 11.4 ¿ 1.3 cm/s, respectively
- however, homozygotes show alterations in aortic arch acceleration suggestive of increased peripheral wave reflections
- anesthetized homozygotes show significantly increased transaortic blood velocities relative to wild-type mice with peak aortic velocity at 133.4 ¿ 7.8 cm/s vs 89.2 ¿ 5.8 cm/s, and mean aortic velocity at 35.9 ¿ 2.7 vs 22.0 ¿ 1.6 cm/s, respectively
- no significant differences in heart rate, peak aortic acceleration or ejection time are observed in the conscious or anesthetized state, when normalized to body weight
- tively

atherosclerotic lesions
- at 24 weeks of age, homozygotes fed a normal diet (but not similarly-fed C57BL/6J control mice) show obvious atherosclerotic lesions in the aortic sinus and ascending aorta
- major lesions are observed on lesser curvature of aortic arch in males and females with minor lesions found at branches of aortic arch
- regular exercise does not reduce atherosclerotic lesion formation in homozygotes, as shown by a comparable % oil red-O staining of whole aortas from sedentary and exercised mutant mice
- at 13 months, homozygotes display atherosclerotic lesions extending from the carotid arteries, heart, and aorta down to the renal arteries and the iliac bifurcation
- plaques in the luminal surface of the aorta are significantly larger in atherosclerotic diet homozygotes than in normal diet homozygotes
- thickened intima, foam cell accumulation and thin collagen cap
- intimal lesions are observed in atherosclerotic aortas in mutants
- the number of atherosclerotic lesions in aortic sinus and ascending aorta is significantly increased in homozygotes fed an atherosclerotic diet vs a normal diet
- 61% covered by plaques at 13 months of age
- 23% of luminal surface in the aortic arch and thoracic aorta is covered by plaques at 4 months of age
- advanced atherosclerotic lesions; massive atheromas with abundant cholesterol crystals, neutral lipids, and diminished extracellular matrix in arotic roots and coronary arteries
- aortic lesions are observed in aortic sinus at level of aortic valve leaflets; lesions are about 27% of total aortal area
- focal fragmentation of elastic laminae
- lesions comprise around 14-16% of total aortic arch area in male and female mutants
- lesions are most severe in the proximal aorta and at the bifurcation of carotid arteries; the proximal carotid arteries are relatively free of lesions

cardiac hypertrophy
- at 13 months, homozygotes show a 59% increase in heart weight-to-body weight ratio relative to wild-type mice

increased heart weight
- at 13 months, homozygotes show a 23% increase in heart weight relative to wild-type mice (186 ¿ 7.1 vs. 151 ¿ 2.5 mg)

abnormal blood-brain barrier function
- impaired blood-brain barrier and blood-nerve barrier as indicated by extensive extravasation of serum proteins into sciatic nerve, spinal cord and cerebellum and occasional extravasation into cortex and subcortex

abnormal blood vessel physiology
- pulse wave velocity is insignificantly elevated at 4 months
- pulse wave velocity significantly elevated at 13 months

decreased susceptibility to atherosclerosis
- in perhexiline-treated mice fed a high-fat diet

increased cardiac output
- under anesthesia, homozygotes exhibit elevated flow velocities suggesting elevated cardiac output

increased susceptibility to atherosclerosis
- on a high fat, high cholesterol diet, mutants exhibit moderate to severe aortic and carotid atherosclerosis
- severity of atherosclerosis is 2-fold and 99-fold higher in atherosclerotic diet homozygotes than in normal diet homozygotes and C57BL/6J control mice, respectively

abnormal spiral modiolar artery morphology
- homozygotes fed an atherosclerotic diet develop atherosclerotic alterations in the spiral modiolar artery (SMA)
- in contrast, no such changes are detected in the SMA of homozygotes fed a normal diet

dilated glomerular capillary
- at times mesangiolysis is associated with ballooning dilatation ("microaneurysm") of adjacent glomerular capillaries

vascular stenosis
- vascular stenosis is significantly increased in homozygotes fed an atherosclerotic diet vs a normal diet

decreased systemic vascular resistance
- under anesthesia, homozygotes appear to exhibit significantly reduced peripheral vascular resistance and compliance in the presence of normal blood pressures

abnormal kidney arterial blood vessel morphology
- arterioles of the vascular pole show a "foamy" degeneration of smooth muscle cells

arteriosclerosis
- homozygotes exhibit a 13% increase in aortic pulse-wave velocity (PWV) relative to wild-type mice (428 ¿ 14.5 cm/s vs 379 ¿ 10.1 cm/s), indicating increased arterial stiffness and reduced vascular elasticity

decreased vasodilation
- homozygotes fed a normal or atherosclerotic diet show severely impaired endothelium-dependent relaxation to acetylcholine in aortic rings relative to age-matched C57BL/6J control mice

kidney microaneurysm
- at times mesangiolysis is associated with ballooning dilatation ("microaneurysm") of adjacent glomerular capillaries

increased cardiac stroke volume
- under anesthesia, homozygotes appear to exhibit significantly increased stroke volume

blood vessel inflammation
- aortae show macrophage and T cell extravasation within atherosclerotic lesions

spiral modiolar artery stenosis
- lumen stenosis of the spiral modiolar artery in the cochlea is exacerbated by an atherosclerotic diet relative to a normal diet

cellular phenotype

increased cholesterol efflux
- in perhexiline-treated mice fed a high-fat diet

abnormal osteoblast physiology
- increased rate of bone formation

oxidative stress
- in contrast, regular exercise results in reduced mitochondrial damage and oxidant load and increased SOD2 and adenine nucleotide translocator activities in normocholesterolemic control mice
- regular exercise fails to reduce endogenous oxidant load and mitochondrial damage in hypercholesterolemic mutant mice

growth/size/body region phenotype

decreased body weight
- at 13 months, homozygotes show a 22% reduction in body weight relative to wild-type mice (34.5 ¿ 0.9 vs. 44.5 ¿ 1.1 g)

cardiac hypertrophy
- at 13 months, homozygotes show a 59% increase in heart weight-to-body weight ratio relative to wild-type mice

decreased body length
- nose to rump length less than controls at both 1 and 3 months

increased heart weight
- at 13 months, homozygotes show a 23% increase in heart weight relative to wild-type mice (186 ¿ 7.1 vs. 151 ¿ 2.5 mg)

increased susceptibility to weight gain
- body weight was less than controls at 3 months but identical at 8 months

increased spleen weight
- increased spleen weight while the thymus weight remains normal

hearing/vestibular/ear phenotype

increased or absent threshold for auditory brainstem response
- at 10 weeks, homozygotes fed a normal diet display higher ABR thresholds than C57BL/6J control mice at all test frequencies, with more hearing loss noted at 32 kHz; by 24 weeks, further hearing loss is detected at all test stimuli levels
- homozygotes fed an atherosclerotic diet show higher ABR thresholds than homozygotes fed a normal diet

organ of Corti degeneration
- at 24 weeks, homozygotes fed a normal diet show significant degeneration of the organ of Corti in the basal turn while the middle turn is relatively normal
- degeneration of the organ of Corti is excerbated by an atherosclerotic diet, with complete loss noted in the basal turn in some animals

abnormal stria vascularis morphology
- on an atherosclerotic diet, homozygotes display a sclerosed and atrophic stria vascularis

cochlear outer hair cell degeneration
- at 24 weeks, homozygotes fed a normal diet show almost complete loss of OHCs in the basal turn and some OHC loss in the middle turn
- OHC loss at the base turn is exacerbated by an atherosclerotic diet

cochlear inner hair cell degeneration
- at 24 weeks, homozygotes fed a normal diet show almost complete loss of IHCs in the basal turn and some IHC loss in the middle turn
- IHC loss at the base turn is exacerbated by an atherosclerotic diet

deafness
- a high positive correlation between ABR thresholds at 16 and 8 kHz, or click and atherosclerotic lesions, and atherosclerotic plaque area of the aorta, and plasma total choelsterol levels is observed in both normal diet and high-fat diet homozygotes
- homozygotes fed a normal diet display hearing loss esp. at high frequencies as compared with C57BL/6J control mice

abnormal cochlea morphology
- endothelial nitric oxide synthase (eNOS) in mutant cochlea is distinctly reduced

abnormal tectorial membrane morphology
- on an atherosclerotic diet, homozygotes display a sclerosed and atrophic tectorial membrane

abnormal basilar membrane morphology
- on an atherosclerotic diet, homozygotes display a sclerosed and atrophic basilar membrane

hematopoietic system phenotype

decreased hematocrit
- Hg)
- at 13 months, awake, unanesthetized homozygotes display slightly but significantly reduced hematocrits ( 11%) relative to wild-type mice at 41.7 ¿ 1.1% vs 46.6 ¿ 0.4%; in contrast, systolic blood pressures remain unaffected (140 ¿ 7.6 mmHg vs 136 ¿ 7.4 mmHg)

increased T-helper 2 cell number

decreased follicular B cell number
- decreased relative to controls

abnormal B cell activation
- spleen cells display polyclonal B cell activation, with increased expression of MHC II, Fas, and CD86 and lower expression of CD21, CD22, and CD23

abnormal CD4-positive, alpha beta T cell number
- clusters of CD4+ cells found in fatty streak lesions
- ratio of Th2 to Th1 cells is increased from 4.4 to 11.4 on a normal diet and up to 20.9 on a high cholesterol diet

increased IgM level
- IgM response to tetanus toxoid is significantly increased as compared to controls

increased marginal zone B cell number
- increased 2-fold compared to wild-type

increased immunoglobulin level
- mutants with cGVH-induced SLE show greatly increased levels compared to wild-type controls or untreated mutants

abnormal T cell number
- increased numbers of cytokine producing T cells

increased B cell number
- newly formed B cells are significantly increased compared to wild-type

increased spleen weight
- increased spleen weight while the thymus weight remains normal

decreased marginal zone B cell number
- with induction of SLE by cGVH, levels are slightly decreased compared to wild-type

Genotype: Apoe^tm1Unc/Apoe^tm1Unc
B6.Cg-Apoe Fas

cardiovascular system phenotype

increased susceptibility to atherosclerosis
- modest increase in total area of lipid deposits in aorta compared to Apoe-null mice

hematopoietic system phenotype

increased immunoglobulin level
- mice display greatly increased levels compared to wild-type controls or Apoe-null mice

homeostasis/metabolism phenotype

increased circulating cholesterol level
- significantly increased relative to wild-type controls or Fas-single mutants at 24 weeks of age; levels are higher than that of B6.129P2-Apoe^tm1Unc

immune system phenotype

increased susceptibility to systemic lupus erythematosus

increased anti-double stranded DNA antibody level
- mice display greatly increased levels compared to wild-type controls or Apoe-null mice

increased immunoglobulin level
- mice display greatly increased levels compared to wild-type controls or Apoe-null mice

increased anti-nuclear antigen antibody level
- mice display greatly increased levels compared to wild-type controls or Apoe-null mice

Genotype: Apoe^tm1Unc/Apoe^tm1Unc
B6.129P2-Apoe

behavior/neurological phenotype

increased food intake
- increased food intake at 12 and 18 months but not earlier

abnormal response to new environment
- mice are less reluctant than wild-type mice to move into an open area
- mice require more time to habituate to a novel environment compared to wild-type mice
- mice consume food slower in a new environment than Tg(GFAP-APOE_i4)#Hol Apoe^tm1Unc/Apoe^tm1Unc and wild-type mice

abnormal kindling response
- after-discharge duration is significantly prolonged by the sixth trial
- delayed rekindling after 3-4 weeks

abnormal thermal nociception
- 41% increase in foot withdrawal latency from painful thermal stimuli
- 100% slower tail withdrawal latency

decreased exploration in new environment
- reduced exploratory behavior in an open field test by 12 months although normal earlier
- exploratory behavior remains constant over several days whereas controls show higher initial exploratory behavior which drops off quickly

abnormal spatial learning
- at 14 to 17 months of age, mice perform better than Tg(GFAP-APOE_i4)#Hol Apoe^tm1Unc/Apoe^tm1Unc and wild-type mice in a rotating holeboard test

abnormal locomotor behavior
- mice spend more time than Tg(GFAP-APOE_i4)#Hol Apoe^tm1Unc/Apoe^tm1Unc in the center of an open field

increased anxiety-related response
- at 6 months as measured in an elevated plus maze

decreased startle reflex

increased fluid intake
- increased water intake at 18 months

cardiovascular system phenotype

atherosclerotic lesions
- cellular composition of lesions is similar among Serpine1-deficient or transgenic, Apoe-deficient genotypes, or Apoe-deficient only mice; at early time points, a greater foam cell content is observed, with more prominent cholesterol clefts and necrotic areas evident with increasing age
- eas evident with increasing age

adipose tissue phenotype

decreased epididymal fat pad weight
- epididymal white fat reduced at both 6 and 18 months

decreased brown adipose tissue mass
- decreased interscapular brown fat at 18 but not at 6 months

endocrine/exocrine gland phenotype

hypersecretion of corticosterone
- elevated adrenal levels at six months but not earlier
- fter 10 min of restraint stress plasma levels are elevated at six months but not at three months

abnormal gland physiology

abnormal adrenal cortex morphology
- increased lipid droplets seen at six months

abnormal adrenal medulla morphology
- increased lipid droplets seen at six months

abnormal adrenal gland morphology

hypopituitarism
- restraint stress at 6 months results in disproportionately low ACTH levels as compared to plasma corticosterone levels

hematopoietic system phenotype

increased CD4-positive, alpha beta T cell number
- mice maintained on a high fat diet and infected with Leishmania major generate more IL-4 and IL-5 producing CD4+ T cells compared to wild-type mice

homeostasis/metabolism phenotype

decreased circulating leptin level
- plasma leptin levels are low at both 6 and 18 months

increased circulating cholesterol level
- 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)

abnormal lipid level
- mice have increased levels of circulating oxidized lipids compared to wild-type mice

immune system phenotype

abnormal dendritic cell physiology
- dendritic cells from mice on a high fat diet are severely impaired in their ability to produce Il-12p40, -12p70, -6, and TNF-alpha compared to dendritic cells from wild-type mice on a high fat diet
- dendrictic cells mount reduced IL-12p40 and TNF-alpha responses to stimulation with zymosan, poly(I:C), LPS, imiquimod, and a combination of anti-CD40 antibodies and CpG compared to wild-type mice but similar to wild-type mice fed a high fat diet
- Normal - however, the immune responses of bone marrow derived dendritic cells from mice fed a high fat diet or splenic dendritic cells from mice fed a regular diet are normal
- Normal - however, CD8alpha+ dendritic cells produce normal amounts of Il-12p70 and -12p40
- in mice fed a high fat diet, dendritic cell production of IL-12p40, IL-6 and TNF-alpha after 35 to 40 weeks, but not after 6 to 10 weeks, is severely impaired compared to wild-type cells in response to CpG/anti-CD-40 stimulation
- CD8alpha-, but not CD8alpha+, dendritic cells are defective in their ability to produce IL-12p40
- mice fed a high fat diet and co-stimulated with CpG or LPS have fewer IL-12p40-producing CD8alpha- dendritic cells (4.6+/-1.1%) than wild-type mice fed a high fat diet (15.3+/-2.4%)

increased susceptibility to parasitic infection
- mice maintained on a high fat diet or regular chow and infected with Leishmania major exhibit an increased swelling and parasitic burden at the site of infection (footpad)
- the immune response of mice fed a high fat diet to Leishmania major infection is skewed towards a Th2-type response
- mice maintained on a high fat diet and infected with Leishmania major produce more IL-4 and IL-5 producing CD4+ T cells compared to wild-type mice

increased CD4-positive, alpha beta T cell number
- mice maintained on a high fat diet and infected with Leishmania major generate more IL-4 and IL-5 producing CD4+ T cells compared to wild-type mice

abnormal cell-mediated immunity
- in an adoptive transfer experiment, the proliferation of Tg(TcrLCMV)2Aox CD45.2+ cell in mice fed a high fat diet and receiving then immunized with GP61-80 peptide with CpG is reduced compared to in wild-type mice similarly treated
- the immune response of mice fed a high fat diet to Leishmania major infection is skewed towards a Th2-type response

nervous system phenotype

abnormal myelin sheath morphology
- blurring of lipid membrane border between axons and Schwann cells
- very little Schwann cell cytoplasm

abnormal sciatic nerve morphology
- reduced number of unmyelinated axons
- ratio of unmyelinated to myelinated axons is reduced
- blurring of lipid membrane border between axons and Schwann cells
- cross-section of unmyelinated axons is irregular
- very little Schwann cell cytoplasm

abnormal kindling response
- delayed rekindling after 3-4 weeks
- after-discharge duration is significantly prolonged by the sixth trial

abnormal synaptic vesicle morphology
- synaptophysin levels are somewhat more reduced than in controls after entorhinal cortex lesion

hypopituitarism
- restraint stress at 6 months results in disproportionately low ACTH levels as compared to plasma corticosterone levels

Genotype: Apoe^tm1Unc/Apoe^tm1Unc
either: B6.129P2-Apoe/J or (involves: 129P2/OlaHsd * C57BL/6J * ICR)

behavior/neurological phenotype

abnormal spatial learning
- 6-month old female mice show subtle learning impairment in water maze task compared to transgenic mutants; 6-month old males show significantly decreased learning ability in the Morris water maze test

decreased vertical activity
- mice have fewer rearing events and shorter rearing times than wild-type controls

mammalian phenotype

nervous system phenotype
- mice show significant loss of synaptophysin-positive presynaptic terminals and neuronal dendrites of the neocortex and hippocampus with age (7-9 months compared to 3-4 months)
- Normal - mice show significant loss of synaptophysin-positive presynaptic terminals and neuronal dendrites of the neocortex and hippocampus with age (7-9 months compared to 3-4 months), similar to wild-type
- Normal - upon 18 mg/kg kainic acid injection, significant loss of neocortical synaptophysin-positive presynaptic terminals and disruption of hippocampal axons are observed, similar to wild-type
- mice exhibit age-dependent loss of synaptophysin-reactive terminals and microtubule-associated protein 2-positive neuronal dendrites in the neocortex and hippocampus
- Normal - mice exhibit age-dependent loss of synaptophysin-reactive terminals and microtubule-associated protein 2-positive neuronal dendrites in the neocortex and hippocampus, similar to wild-type

behavior/neurological phenotype
- Normal - no alterations in passive avoidance learning are observed; coordination levels measured in rotorod tests are similar to wild-type

Phenotype Information

Body Weight Information - JAX^® Mice Strain B6.129P2-Apoe^tm1Unc/J (002052)
Body Weight Information - JAX^® Mice Strain - B6.129P2-Apoe^tm1Unc/J (002052)
Cardiovascular Disease Phenotypes
JAX^® Physiological Data Summary [pdf]

References

Piedrahita JA; Zhang SH; Hagaman JR; Oliver PM; Maeda N. 1992. Generation of mice carrying a mutant apolipoprotein E gene inactivated by gene targeting in embryonic stem cells. Proc Natl Acad Sci U S A 89(10):4471-5PubMed: 1584779 MGI: J:1050

Additional References

Ando Y; Shimizugawa T; Takeshita S; Ono M; Shimamura M; Koishi R; Furukawa H. 2003. A decreased expression of angiopoietin-like 3 is protective against atherosclerosis in apoE-deficient mice. J Lipid Res 44(6):1216-23PubMed: 12671033 MGI: J:84022
Brecht WJ; Harris FM; Chang S; Tesseur I; Yu GQ; Xu Q; Dee Fish J; Wyss-Coray T; Buttini M; Mucke L; Mahley RW; Huang Y. 2004. Neuron-specific apolipoprotein e4 proteolysis is associated with increased tau phosphorylation in brains of transgenic mice. J Neurosci 24(10):2527-34PubMed: 15014128 MGI: J:90126
Brionne TC; Tesseur I; Masliah E; Wyss-Coray T. 2003. Loss of TGF-beta1 leads to increased neuronal cell death and microgliosis in mouse brain. Neuron 40(6):1133-45PubMed: 14687548 MGI: J:87148
Bruemmer D; Collins AR; Noh G; Wang W; Territo M; Arias-Magallona S; Fishbein MC; Blaschke F; Kintscher U; Graf K; Law RE; Hsueh WA. 2003. Angiotensin II-accelerated atherosclerosis and aneurysm formation is attenuated in osteopontin-deficient mice. J Clin Invest 112(9):1318-31PubMed: 14597759 MGI: J:86531
Burnett MS; Gaydos CA; Madico GE; Glad SM; Paigen B; Quinn TC; Epstein SE. 2001. Atherosclerosis in apoE knockout mice infected with multiple pathogens. J Infect Dis 183(2):226-231PubMed: 11120928 MGI: J:66879
Chen Z; Fitzgerald RL; Schonfeld G. 2002. Hypobetalipoproteinemic Mice with a Targeted Apolipoprotein (Apo) B-27.6-specifying Mutation. IN VIVO EVIDENCE FOR AN IMPORTANT ROLE OF AMINO ACIDS 1254-1744 OF ApoB IN LIPID TRANSPORT AND METABOLISM OF THE ApoB-CONTAINING LIPOPROTEIN. J Biol Chem 277(16):14135-45PubMed: 11839763 MGI: J:76047
Cuff CA; Kothapalli D; Azonobi I; Chun S; Zhang Y; Belkin R; Yeh C; Secreto A; Assoian RK; Rader DJ; Pure E. 2001. The adhesion receptor CD44 promotes atherosclerosis by mediating inflammatory cell recruitment and vascular cell activation. J Clin Invest 108(7):1031-40PubMed: 11581304 MGI: J:72315
Davisson RL; Yang G; Beltz TG; Cassell MD; Johnson AK; Sigmund CD. 1998. The brain renin-angiotensin system contributes to the hypertension in mice containing both the human renin and human angiotensinogen transgenes. Circ Res 83(10):1047-58PubMed: 9815152 MGI: J:79945
Dolev I; Michaelson DM. 2004. A nontransgenic mouse model shows inducible amyloid-beta (Abeta) peptide deposition and elucidates the role of apolipoprotein E in the amyloid cascade. Proc Natl Acad Sci U S A 101(38):13909-14PubMed: 15365176 MGI: J:92619
Fan YY; Ramos KS; Chapkin RS. 2001. Dietary gamma-linolenic acid suppresses aortic smooth muscle cell proliferation and modifies atherosclerotic lesions in apolipoprotein E knockout mice. J Nutr 131(6):1675-81PubMed: 11385052 MGI: J:69821
Febbraio M; Podrez EA; Smith JD; Hajjar DP; Hazen SL; Hoff HF; Sharma K; Silverstein RL. 2000. Targeted disruption of the class B scavenger receptor CD36 protects against atherosclerotic lesion development in mice [see comments] J Clin Invest 105(8):1049-56PubMed: 10772649 MGI: J:61672
Guo Z; Mitchell-Raymundo F; Yang H; Ikeno Y; Nelson J; Diaz V; Richardson A; Reddick R. 2002. Dietary restriction reduces atherosclerosis and oxidative stress in the aorta of apolipoprotein E-deficient mice. Mech Ageing Dev 123(8):1121-31PubMed: 12044962 MGI: J:76930
Han Z; Truong QA; Park S; Breslow JL. 2003. Two Hsp70 family members expressed in atherosclerotic lesions. Proc Natl Acad Sci U S A 100(3):1256-61PubMed: 12552099 MGI: J:81835
Harry GJ; Lefebvre d'Hellencourt C; Bruccoleri A; Schmechel D. 2000. Age-dependent cytokine responses: trimethyltin hippocampal injury in wild-type, APOE knockout, and APOE4 mice. Brain Behav Immun 14(4):288-304PubMed: 11120597 MGI: J:66874
Hirano T; Takahashi T; Saito S; Tajima H; Ebara T; Adachi M. 2001. Apoprotein C-III deficiency markedly stimulates triglyceride secretion in vivo: comparison with apoprotein E. Am J Physiol Endocrinol Metab 281(4):E665-9PubMed: 11551841 MGI: J:72104
Holm TM; Braun A; Trigatti BL; Brugnara C; Sakamoto M; Krieger M; Andrews NC. 2002. Failure of red blood cell maturation in mice with defects in the high-density lipoprotein receptor SR-BI. Blood 99(5):1817-24PubMed: 11861300 MGI: J:75090
Huo Y; Schober A; Forlow SB; Smith DF; Hyman MC; Jung S; Littman DR; Weber C; Ley K. 2003. Circulating activated platelets exacerbate atherosclerosis in mice deficient in apolipoprotein E. Nat Med 9(1):61-7PubMed: 12483207 MGI: J:81164
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
Ishiguro H; Yoshida H; Major AS; Zhu T; Babaev VR; Linton MF; Fazio S. 2001. Retrovirus-mediated expression of apolipoprotein A-I in the macrophage protects against atherosclerosis in vivo. J Biol Chem 276(39):36742-8PubMed: 11477092 MGI: J:71811
Ishimori N; Iwabuchi K; Fujii S; Watano K; Iwabuchi C; Ato M; Chiba H; Tanaka S; Kitabatake A; Onoe K. 2001. Mixed allogeneic chimerism with wild-type strains ameliorates atherosclerosis in apolipoprotein E-deficient mice. J Leukoc Biol 69(5):732-40PubMed: 11358981 MGI: J:69647
Joyce CW; Amar MJ; Lambert G; Vaisman BL; Paigen B; Najib-Fruchart J; Hoyt RF Jr; Neufeld ED; Remaley AT; Fredrickson DS; Brewer HB Jr; Santamarina-Fojo S. 2002. The ATP binding cassette transporter A1 (ABCA1) modulates the development of aortic atherosclerosis in C57BL/6 and apoE-knockout mice. Proc Natl Acad Sci U S A 99(1):407-12PubMed: 11752403 MGI: J:73704
Kauser K; da Cunha V; Fitch R; Mallari C; Rubanyi GM. 2000. Role of endogenous nitric oxide in progression of atherosclerosis in apolipoprotein E-deficient mice. Am J Physiol Heart Circ Physiol 278(5):H1679-85PubMed: 10775149 MGI: J:62352
Kirk EA; Heinecke JW; LeBoeuf RC. 2001. Iron overload diminishes atherosclerosis in apoE-deficient mice. J Clin Invest 107(12):1545-53PubMed: 11413162 MGI: J:70613
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
Miura Y; Chiba T; Tomita I; Koizumi H; Miura S; Umegaki K; Hara Y; Ikeda M; Tomita T. 2001. Tea catechins prevent the development of atherosclerosis in apoprotein E-deficient mice. J Nutr 131(1):27-32PubMed: 11208934 MGI: J:66898
Moghadasian MH; McManus BM; Nguyen LB; Shefer S; Nadji M; Godin DV; Green TJ; Hill J; Yang Y; Scudamore CH; Frohlich JJ. 2001. Pathophysiology of apolipoprotein E deficiency in mice: relevance to apo E-related disorders in humans. FASEB J 15(14):2623-30PubMed: 11726538 MGI: J:73202
Ong JM; Zorapapel NC; Aoki AM; Brown DJ; Nesburn AB; Rich KA; Kenney CM. 2003. Impaired electroretinogram (ERG) response in apolipoprotein E-deficient mice. Curr Eye Res 27(1):15-24PubMed: 12868005 MGI: J:84688
Patel S; Thelander EM; Hernandez M; Montenegro J; Hassing H; Burton C; Mundt S; Hermanowski-Vosatka A; Wright SD; Chao YS; Detmers PA. 2001. ApoE(-/-) mice develop atherosclerosis in the absence of complement component C5. Biochem Biophys Res Commun 286(1):164-70PubMed: 11485323 MGI: J:71193
Ramassamy C; Krzywkowski P; Averill D; Lussier-Cacan S; Theroux L; Christen Y; Davignon J; Poirier J. 2001. Impact of apoE deficiency on oxidative insults and antioxidant levels in the brain. Brain Res Mol Brain Res 86(1-2):76-83PubMed: 11165374 MGI: J:67204
Rothstein NM; Quinn TC; Madico G; Gaydos CA; Lowenstein CJ. 2001. Effect of azithromycin on murine arteriosclerosis exacerbated by Chlamydia pneumoniae. J Infect Dis 183(2):232-238PubMed: 11120929 MGI: J:66880
Sakaguchi T; Yan SF; Yan SD; Belov D; Rong LL; Sousa M; Andrassy M; Marso SP; Duda S; Arnold B; Liliensiek B; Nawroth PP; Stern DM; Schmidt AM; Naka Y. 2003. Central role of RAGE-dependent neointimal expansion in arterial restenosis. J Clin Invest 111(7):959-72PubMed: 12671045 MGI: J:82620
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
Shih DM; Xia YR; Wang XP; Miller E; Castellani LW; Subbanagounder G; Cheroutre H; Faull KF; Berliner JA; Witztum JL; Lusis AJ. 2000. Combined serum paraoxonase knockout/apolipoprotein E knockout mice exhibit increased lipoprotein oxidation and atherosclerosis. J Biol Chem 275(23):17527-35PubMed: 10748217 MGI: J:62750
van Haperen R; de Waard M; van Deel E; Mees B; Kutryk M; van Aken T; Hamming J; Grosveld F; Duncker DJ; de Crom R. 2002. Reduction of blood pressure, plasma cholesterol, and atherosclerosis by elevated endothelial nitric oxide. J Biol Chem 277(50):48803-7PubMed: 12364322 MGI: J:80701
Wang H; Jiang X; Yang F; Gaubatz JW; Ma L; Magera MJ; Yang X; Berger PB; Durante W; Pownall HJ; Schafer AI. 2003. Hyperhomocysteinemia accelerates atherosclerosis in cystathionine beta-synthase and apolipoprotein E double knock-out mice with and without dietary perturbation. Blood 101(10):3901-7PubMed: 12506016 MGI: J:83449
Xia M; Ling WH; Ma J; Kitts DD; Zawistowski J. 2003. Supplementation of diets with the black rice pigment fraction attenuates atherosclerotic plaque formation in apolipoprotein e deficient mice. J Nutr 133(3):744-51PubMed: 12612147 MGI: J:82218
Zhang SH; Reddick RL; Piedrahita JA; Maeda N. 1992. Spontaneous hypercholesterolemia and arterial lesions in mice lacking apolipoprotein E. Science 258(5081):468-71PubMed: 1411543 MGI: J:16573
Zhou Y; Elkins PD; Howell LA; Ryan DH; Harris RB. 1998. Apolipoprotein-E deficiency results in an altered stress responsiveness in addition to an impaired spatial memory in young mice. Brain Res 788(1-2):151-9PubMed: 9554991 MGI: J:47604

Additional - Apoe^tm1Unc related

Technical Support

CONTACT TECHNICAL SUPPORT

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

This strain is a good breeder.
- Additional Breeding and Husbandry Support
Mating System
- Homozygote x Homozygote
Appearance
- black
  Related Genotype: a/a
Citation
When using the ApoE KO mouse strain in a publication, please cite the originating article(s) and include JAX stock #002052 in your Materials and Methods section.

Animal Health Reports

Facility Barrier Level Descriptions

MP14 (Maximum)

RB15 (Maximum)

Pricing & Availability

Readily Available

Domestic
International

Live Mouse

Age

Genotype

Price

weeks

Cryorecovery - Pricing

Service/Product	Description	Price
> >	Please inquire

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

Also Known As:ApoE KO

Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Control Suggestions

Additional Information

Selected References

Apoetm1Unc

Allele Symbol: Apoetm1Unc

Disease Terms

Research Areas By Phenotype

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

Genotype: Apoetm1Unc related

Mammalian Phenotype Terms by Genotype

Genotype: Apoetm1Unc/Apoetm1Uncinvolves: 129P2/OlaHsd

muscle phenotype

nervous system phenotype

behavior/neurological phenotype

cardiovascular system phenotype

homeostasis/metabolism phenotype

Genotype: Apoetm1Unc/Apoetm1Uncinvolves: 129P2/OlaHsd * C57BL/6 * DBA

homeostasis/metabolism phenotype

Genotype: Apoetm1Unc/Apoetm1Uncinvolves: 129P2/OlaHsd * C57BL/6

homeostasis/metabolism phenotype

immune system phenotype

nervous system phenotype

respiratory system phenotype

cardiovascular system phenotype

Genotype: Apoetm1Unc/Apoetm1Uncinvolves: 129P2/OlaHsd * C57BL/6 * FVB/N

cardiovascular system phenotype

Genotype: Apoetm1Unc/Apoetm1Uncinvolves: 129P2/OlaHsd * 129S4/SvJae * C57BL/6

cardiovascular system phenotype

Genotype: Apoetm1Unc/Apoe+involves: 129P2/OlaHsd * C57BL/6

homeostasis/metabolism phenotype

Genotype: Apoetm1Unc/Apoetm1UncB6.129P2-Apoe/J

behavior/neurological phenotype

homeostasis/metabolism phenotype

immune system phenotype

integument phenotype

liver/biliary system phenotype

mortality/aging

muscle phenotype

nervous system phenotype

renal/urinary system phenotype

respiratory system phenotype

skeleton phenotype

taste/olfaction phenotype

vision/eye phenotype

cardiovascular system phenotype

cellular phenotype

growth/size/body region phenotype

hearing/vestibular/ear phenotype

hematopoietic system phenotype

Genotype: Apoetm1Unc/Apoetm1UncB6.Cg-Apoe Fas

cardiovascular system phenotype

hematopoietic system phenotype

homeostasis/metabolism phenotype

immune system phenotype

Genotype: Apoetm1Unc/Apoetm1UncB6.129P2-Apoe

behavior/neurological phenotype

cardiovascular system phenotype

adipose tissue phenotype

endocrine/exocrine gland phenotype

hematopoietic system phenotype

homeostasis/metabolism phenotype

immune system phenotype

nervous system phenotype

Genotype: Apoetm1Unc/Apoetm1Unceither: B6.129P2-Apoe/J or (involves: 129P2/OlaHsd * C57BL/6J * ICR)

behavior/neurological phenotype

mammalian phenotype

Phenotype Information

References

Additional References

Additional - Apoetm1Unc related

Genotyping Protocols

Dietary Information

Breeding Considerations

Apoe^tm1Unc

Allele Symbol: Apoe^tm1Unc

Genotype: Apoe^tm1Unc related

Genotype: Apoe^tm1Unc/Apoe^tm1Unc
involves: 129P2/OlaHsd

Genotype: Apoe^tm1Unc/Apoe^tm1Unc
involves: 129P2/OlaHsd * C57BL/6 * DBA

Genotype: Apoe^tm1Unc/Apoe^tm1Unc
involves: 129P2/OlaHsd * C57BL/6

Genotype: Apoe^tm1Unc/Apoe^tm1Unc
involves: 129P2/OlaHsd * C57BL/6 * FVB/N

Genotype: Apoe^tm1Unc/Apoe^tm1Unc
involves: 129P2/OlaHsd * 129S4/SvJae * C57BL/6

Genotype: Apoe^tm1Unc/Apoe⁺
involves: 129P2/OlaHsd * C57BL/6

Genotype: Apoe^tm1Unc/Apoe^tm1Unc
B6.129P2-Apoe/J

Genotype: Apoe^tm1Unc/Apoe^tm1Unc
B6.Cg-Apoe Fas

Genotype: Apoe^tm1Unc/Apoe^tm1Unc
B6.129P2-Apoe

Genotype: Apoe^tm1Unc/Apoe^tm1Unc
either: B6.129P2-Apoe/J or (involves: 129P2/OlaHsd * C57BL/6J * ICR)

Additional - Apoe^tm1Unc related