JAX Mice Database - 002052 B6.129P2-Apoe<tm1Unc>/J

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Strain Name:	B6.129P2-Apoe^tm1Unc/J
Stock Number:	002052
Availability:	Level 1

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General Terms and Conditions

Genes & Alleles

Apoe; Apoe^tm1Unc;

Product Information

Strain Details

Type JAX^® GEMM^® Strain - Congenic

Additional information on JAX^® GEMM^® Strains.

Type JAX^® GEMM^® Strain - Mutant Strain

Type JAX^® GEMM^® Strain - Targeted Mutation

Mating System Homozygote x Homozygote (Female x Male)

Species laboratory mouse

Background Strain C57BL/6

Donor Strain 129P2 via E14TG2a ES cell line

Donating Investigator Nobuyo Maeda, Univ of North Carolina at Chapel Hill

Generation N12F17 (03-JAN-08)

Appearance
black
Related Genotype: a/a
Strain 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. Recent studies indicate that APOE deficient mice have altered responses to stress, impaired spatial learning and memory, altered long term potentiation, and synaptic damage.
Strain 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 129-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. The C57BL/6J strain was produced by backcrossing the Apoe^tm1Unc mutation 10 times to C57BL/6J mice. Previously mice backcrossed 6 times (N6) to C57BL/6J mice were distributed solely. Mice from the N6 generation are homozygous for pink-eyed dilution p giving them pink eyes and a silver coat color. The E14Tg2a ES cell line carries this recessive mutation which remains linked to the targeted Apoe gene on Chromosome 7 at this backcross generation. Mice from the N6 colony are no longer available for distribution.

Mammalian Phenotype Terms assigned by genotype

Apoe^tm1Unc/Apoe^tm1Unc
B6.129P2-Apoe^tm1Unc/J
life span-post-weaning/aging

premature death (MGI Ref ID J:73202)

35% dead by 18 months

cardiovascular system phenotype

abnormal aorta morphology (MGI Ref ID J:101576)

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

the number of atherosclerotic lesions in aortic sinus and ascending aorta is significantly increased in homozygotes fed an atherosclerotic diet vs a normal diet

endothelial nitric oxide synthase (eNOS) in mutant aortic wall is distinctly reduced

abnormal blood flow velocity (MGI Ref ID J:108154)

anesthetized homozygotes show significantly increased transaortic blood velocities relative to wild type mice with peak aortic velocity at 133.4 ą 7.8 cm/s vs 89.2 ą 5.8 cm/s, and mean aortic velocity at 35.9 ą 2.7 vs 22.0 ą 1.6 cm/s, respectively

in addition, anesthetized homozygotes show significantly increased transmitral blood velocities relative to wild type mice with peak mitral velocities at 92 ą 7.2 cm/s vs 47.2 ą 5.3 cm/s, and mean mitral velocities at 20.6 ą 1.7 vs 11.4 ą 1.3 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

however, homozygotes show alterations in aortic arch acceleration suggestive of increased peripheral wave reflections

abnormal blood vessel physiology (MGI Ref ID J:60364)

pulse wave velocity is insignificantly elevated at 4 months

pulse wave velocity significantly elevated at 13 months

abnormal blood-brain barrier function (MGI Ref ID J:69455)

impairment of blood-brain barrier (BBB) function

impairment of blood-nerve barrier (BNB) function

atherosclerotic lesions (MGI Ref ID J:133606)

advanced atherosclerotic lesions

at 13 months, homozygotes display atherosclerotic lesions extending from the carotid arteries, heart, and aorta down to the renal arteries and the iliac bifurcation

lesions are most severe in the proximal aorta and at the bifurcation of carotid arteries; the proximal carotid arteries are relatively free of lesions

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 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

the number of atherosclerotic lesions in aortic sinus and ascending aorta is significantly increased in homozygotes fed an atherosclerotic diet vs a normal diet

plaques in the luminal surface of the aorta are significantly larger in atherosclerotic diet homozygotes than in normal diet homozygotes

23% of luminal surface in the aortic arch and thoracic aorta is covered by plaques at 4 months of age

61% covered by plaques at 13 months of age

thickened intima, foam cell accumulation and thin collagen cap

focal fragmentation of elastic laminae

intimal lesions are observed in atherosclerotic aortas in mutants

increased susceptibility to atherosclerosis (MGI Ref ID J:101576)

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

decreased vasodilation (MGI Ref ID J:101576)

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

vascular stenosis (MGI Ref ID J:101576)

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

spiral modiolar artery stenosis (MGI Ref ID J:101576)

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

abnormal cardiac stroke volume (MGI Ref ID J:108154)

under anesthesia, homozygotes appear to exhibit significantly increased stroke volume

abnormal spiral modiolar artery morphology (MGI Ref ID J:101576)

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

arteriosclerosis (MGI Ref ID J:108154)

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

atherosclerotic lesions (MGI Ref ID J:133606)

advanced atherosclerotic lesions

at 13 months, homozygotes display atherosclerotic lesions extending from the carotid arteries, heart, and aorta down to the renal arteries and the iliac bifurcation

lesions are most severe in the proximal aorta and at the bifurcation of carotid arteries; the proximal carotid arteries are relatively free of lesions

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 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

the number of atherosclerotic lesions in aortic sinus and ascending aorta is significantly increased in homozygotes fed an atherosclerotic diet vs a normal diet

plaques in the luminal surface of the aorta are significantly larger in atherosclerotic diet homozygotes than in normal diet homozygotes

23% of luminal surface in the aortic arch and thoracic aorta is covered by plaques at 4 months of age

61% covered by plaques at 13 months of age

thickened intima, foam cell accumulation and thin collagen cap

focal fragmentation of elastic laminae

intimal lesions are observed in atherosclerotic aortas in mutants

increased susceptibility to atherosclerosis (MGI Ref ID J:101576)

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

cardiac hypertrophy (MGI Ref ID J:108154)

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

decreased systemic vascular resistance (MGI Ref ID J:108154)

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

increased cardiac output (MGI Ref ID J:108154)

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

increased heart weight (MGI Ref ID J:108154)

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

muscle phenotype

impaired muscle relaxation (MGI Ref ID J:60364)

relaxation response to acetylcholine in blood vessels is significantly attenuated at 13 months of age

maximal response to acetylcholine is considerably reduced

homeostasis/metabolism phenotype

abnormal circulating cholesterol level (MGI Ref ID J:73202)

decreased HDL/total cholesterol ratio

decreased HDL/LDL ratio

increased circulating cholesterol level (MGI Ref ID J:73202)

increasing with age

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

on a normal diet, homozygotes display significantly increased plasma total cholesterol (TC) levels relative to C57BL/6J control mice

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

total serum cholesterol 70 fold higher than controls on a normal diet

total serum cholesterol 20 fold higher than controls on high fat diet where controls show 4 fold increase over normal diet

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

increased circulating LDL cholesterol level (MGI Ref ID J:93987)

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

increased circulating VLDL cholesterol level (MGI Ref ID J:93987)

on a normal diet, homozygotes display significantly increased plasma VLDL cholesterol levels relative to C57BL/6J control mice

on an atherosclerotic diet, homozygotes show a further significant increase in plasma VLDL cholesterol levels relative to homozygotes on a normal diet

abnormal circulating homocysteine level (MGI Ref ID J:73202)

decreased plasma total homocysteine levels

decreased circulating glucose level (MGI Ref ID J:73202)

in plasma

decreased circulating triglyceride level (MGI Ref ID J:93987)

hyperlipidemia (MGI Ref ID J:101576)

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

increased circulating triglyceride level (MGI Ref ID J:73202)

in plasma

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

skin/coat/nails phenotype

skin lesions (MGI Ref ID J:73202)

eruptive xanthomas on shoulder and back areas with lipids and extracellular matix as the predominant components

growth/size phenotype

decreased body length (MGI Ref ID J:136630)

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

decreased body weight (MGI Ref ID J:60364)

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

increased weight gain (MGI Ref ID J:136630)

body weight was less than controls at 3 months but identical at 8 months

hematopoietic system phenotype

abnormal B cell activation (MGI Ref ID J:133606)

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 T cell number (MGI Ref ID J:47027)

increased numbers of cytokine producing T cells

abnormal CD4-positive T cell number (MGI Ref ID J:108154)

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 T-helper 2 cell number (MGI Ref ID J:47027)

decreased follicular B cell number (MGI Ref ID J:133606)

decreased relative to controls

decreased hematocrit (MGI Ref ID J:108154)

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

decreased marginal zone B cell number (MGI Ref ID J:133606)

with induction of SLE by cGVH, levels are slightly decreased compared to wild-type

increased B cell number (MGI Ref ID J:133606)

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

increased marginal zone B cell number (MGI Ref ID J:133606)

increased 2-fold compared to wild-type

increased spleen weight (MGI Ref ID J:61564)

increased spleen weight while the thymus weight remains normal

cellular phenotype

oxidative stress (MGI Ref ID J:97385)

regular exercise fails to reduce endogenous oxidant load and mitochondrial damage in hypercholesterolemic mutant mice

in contrast, regular exercise results in reduced mitochondrial damage and oxidant load and increased SOD2 and adenine nucleotide translocator activities in normocholesterolemic control mice

hearing/vestibular/ear phenotype

abnormal cochlea morphology (MGI Ref ID J:101576)

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

abnormal basilar membrane (MGI Ref ID J:101576)

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

abnormal stria vascularis (MGI Ref ID J:101576)

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

abnormal tectorial membrane morphology (MGI Ref ID J:101576)

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

cochlear inner hair cell degeneration (MGI Ref ID J:101576)

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

cochlear outer hair cell degeneration (MGI Ref ID J:101576)

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

organ of Corti degeneration (MGI Ref ID J:101576)

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

deafness (MGI Ref ID J:101576)

homozygotes fed a normal diet display hearing loss esp. at high frequencies as compared with C57BL/6J control mice

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

decreased brainstem auditory evoked potential (MGI Ref ID J:101576)

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

nervous system phenotype

abnormal blood-brain barrier function (MGI Ref ID J:69455)

impairment of blood-brain barrier (BBB) function

impairment of blood-nerve barrier (BNB) function

cochlear ganglion degeneration (MGI Ref ID J:101576)

at 24 weeks, homozygotes fed a normal diet show a reduced number of spiral ganglion cells in the basal turn of the cochlea

loss of ganglion cells is excerbated by an atherosclerotic diet

cochlear inner hair cell degeneration (MGI Ref ID J:101576)

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

cochlear outer hair cell degeneration (MGI Ref ID J:101576)

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

immune system phenotype

abnormal immune system morphology (MGI Ref ID J:47027)

abnormal B cell activation (MGI Ref ID J:133606)

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 T cell number (MGI Ref ID J:47027)

increased numbers of cytokine producing T cells

abnormal CD4-positive T cell number (MGI Ref ID J:108154)

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 T-helper 2 cell number (MGI Ref ID J:47027)

decreased follicular B cell number (MGI Ref ID J:133606)

decreased relative to controls

decreased marginal zone B cell number (MGI Ref ID J:133606)

with induction of SLE by cGVH, levels are slightly decreased compared to wild-type

increased B cell number (MGI Ref ID J:133606)

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

increased marginal zone B cell number (MGI Ref ID J:133606)

increased 2-fold compared to wild-type

increased spleen weight (MGI Ref ID J:61564)

increased spleen weight while the thymus weight remains normal

abnormal immune system physiology (MGI Ref ID J:61564)

abnormal B cell activation (MGI Ref ID J:133606)

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 immune serum protein physiology (MGI Ref ID J:61564)

decreased interferon-gamma secretion (MGI Ref ID J:47027)

production is reduced when fed a high cholesterol diet

increased immunoglobulin level (MGI Ref ID J:133606)

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

increased IgM level (MGI Ref ID J:61564)

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

decreased susceptibility to type IV hypersensitivity reaction (MGI Ref ID J:61564)

decreased antigen specific delayed hypersensitivity response

increased autoantibody level (MGI Ref ID J:133606)

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

increased anti-nuclear antigen antibody level (MGI Ref ID J:133606)

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

increased anti-double stranded DNA antibody level (MGI Ref ID J:133606)

after induction of cGVH-SLE, mice display greatly increased levels compared to wild-type controls or non-cGVH-SLE mutants

increased susceptibility to systemic lupus erythematosus (MGI Ref ID J:133606)

behavior/neurological phenotype

abnormal spatial learning (MGI Ref ID J:120203)

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 (MGI Ref ID J:120203)

elevated thigmotaxis in Morris maze tests

renal/urinary system phenotype

abnormal renal glomerulus morphology (MGI Ref ID J:125978)

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

lipid droplets filling glomerular capillary lumina at 36 weeks in about 50% of mice

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

increased glomerular tuft area

glomerular cell numbers are increased

liver/biliary system phenotype

abnormal liver physiology (MGI Ref ID J:104609)

no significant change in serum alanine transaminase with high fat diet as is seen in controls (marker for liver damage)

hepatic uptake of LDL is increased two fold

vision/eye phenotype

abnormal eye electrophysiology (MGI Ref ID J:84688)

implicit times increased for a and b waves of dark adapted electroretinogram

wave amplitudes attenuated for a and b waves of dark adapted electroretinogram

abnormal retinal inner nuclear layer morphology (MGI Ref ID J:70245)

perinuclear vacuolation on a high cholesterol diet

thin retinal inner nuclear layer (MGI Ref ID J:70245)

cell numbers reduced

thin retinal outer nuclear layer (MGI Ref ID J:70245)

cell numbers reduced

taste/olfaction phenotype

impaired olfaction (MGI Ref ID J:89344)

preference for plain water over 0.1% iso-amyl alcohol moderate compared to the strong preference shown by controls

slower than control to find buried food pellet although found pellets visually more rapidly

latency to taste vanillin-cued quinine significantly increased only at day 5

skeleton phenotype

abnormal bone structure (MGI Ref ID J:111209)

abnormal cancellous bone morphology (MGI Ref ID J:111209)

increased number of trabeculae

increased bone density (MGI Ref ID J:111209)

higher bone mineralization density in vertebral bodies

increased bone volume to tissue volume ratio

increased cortical bone thickness (MGI Ref ID J:111209)

in vertebral bodies and tibia

abnormal skeleton physiology (MGI Ref ID J:111209)

abnormal osteoblast physiology (MGI Ref ID J:111209)

increased rate of bone formation

increased bone density (MGI Ref ID J:111209)

higher bone mineralization density in vertebral bodies

increased bone volume to tissue volume ratio

respiratory system phenotype

abnormal respiratory alveoli morphology (MGI Ref ID J:136630)

fewer but larger alveoli at 3 months of age

less surface area to volume

abnormal respiratory function (MGI Ref ID J:136630)

percent increase in hysteresivity with age greater than in controls

abnormal airway resistance (MGI Ref ID J:136630)

resistance to airflow greater than controls at 3months but not at 8 months

abnormal lung capacity (MGI Ref ID J:136630)

lung volume similar to controls at 3months but 2.5 fold greater at 8 months

abnormal lung compliance (MGI Ref ID J:136630)

dynamic and static compliance greater than controls at 8 months

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

*normal* behavior/neurological phenotype (MGI Ref ID J:100975)

no alterations in passive avoidance learning are observed; coordination levels measured in rotorod tests are similar to wild-type

abnormal spatial learning (MGI Ref ID J:100975)

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 (MGI Ref ID J:100975)

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

nervous system phenotype

*normal* nervous system phenotype (MGI Ref ID J:100975)

mice exhibit age-dependent loss of synaptophysin-reactive terminals and microtubule-associated protein 2-positive neuronal dendrites in the neocortex and hippocampus 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

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 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) 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

Apoe^tm1Unc/Apoe^tm1Unc
B6.129P2-Apoe^tm1Unc
immune system phenotype

abnormal cell-mediated immunity (MGI Ref ID J:125366)

the immune response of mice fed a high fat diet to Leishmania major infection is skewed towards a Th2-type response

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

abnormal dendritic cell physiology (MGI Ref ID J:125366)

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

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

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

however, CD8alpha+ dendritic cells produce normal amounts of Il-12p70 and -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%)

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

increased CD4-positive T cell number (MGI Ref ID J:125366)

mice maintained on a high fat diet and infect with Leishmania major generate more IL-4 and IL-5 producing CD4+ T cells compared to wild type mice

increased susceptibility to parasitic infection (MGI Ref ID J:125366)

mice maintained on a high fat diet and infect with Leishmania major produce more IL-4 and IL-5 producing CD4+ T cells compared to wild type mice

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 or regular chow and infect with Leishmania major exhibit an increased swelling and parasitic burden at the site of infection (footpad)

homeostasis/metabolism phenotype

abnormal lipid level (MGI Ref ID J:125366)

mice have increased levels of circulating oxidized lipids compared to wild type mice

decreased circulating leptin level (MGI Ref ID J:60585)

plasma leptin levels are low at both 6 and 18 months

behavior/neurological phenotype

abnormal eating/drinking behavior (MGI Ref ID J:60585)

increased drinking behavior (MGI Ref ID J:60585)

increased water intake at 18 months

increased eating behavior (MGI Ref ID J:60585)

increased food intake at 12 and 18 months but not earlier

abnormal locomotor activity (MGI Ref ID J:71062)

mice spend more time than Tg(GFAP-APOE*4)Hol Apoe^tm1Unc/Apoe^tm1Unc in the center of an open field

abnormal response to new environment (MGI Ref ID J:71062)

mice consume food slower in a new environment than Tg(GFAP-APOE*4)Hol Apoe^tm1Unc/Apoe^tm1Unc and wild type mice

mice require more time to habituate to a novel environment compared to wild type mice

mice are less reluctant than wild type mice to move into an open area

decreased exploration in new environment (MGI Ref ID J:60585)

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 (MGI Ref ID J:71062)

at 14 to 17 months of age, mice perform better than Tg(GFAP-APOE*4)Hol Apoe^tm1Unc/Apoe^tm1Unc and wild type mice in a rotating holeboard test

abnormal thermal nociception (MGI Ref ID J:106368)

41% increase in foot withdrawal latency from painful thermal stimuli

100% slower tail withdrawal latency

decreased startle reflex (MGI Ref ID J:71062)

increased anxiety-related response (MGI Ref ID J:60585)

at 6 months as measured in an elevated "+" maze

kindling (MGI Ref ID J:118390)

after-discharge duration is significantly prolonged by the sixth trial

delayed rekindling after 3-4 weeks

hearing/vestibular/ear phenotype

decreased startle reflex (MGI Ref ID J:71062)

hematopoietic system phenotype

increased CD4-positive T cell number (MGI Ref ID J:125366)

mice maintained on a high fat diet and infect with Leishmania major generate more IL-4 and IL-5 producing CD4+ T cells compared to wild type mice

nervous system phenotype

abnormal myelin sheath morphology (MGI Ref ID J:106368)

very little Schwann cell cytoplasm

blurring of lipid membrane border between axons and Schwann cells

abnormal sciatic nerve (MGI Ref ID J:106368)

cross-section of unmyelinated axons is irregular

very little Schwann cell cytoplasm

blurring of lipid membrane border between axons and Schwann cells

reduced number of unmyelinated axons

ratio of unmyelinated to myelinated axons is reduced

abnormal synaptic vesicle morphology (MGI Ref ID J:118390)

synaptophysin levels are somewhat more reduced than in controls after entorhinal cortex lesion

kindling (MGI Ref ID J:118390)

after-discharge duration is significantly prolonged by the sixth trial

delayed rekindling after 3-4 weeks

touch/vibrissae phenotype

abnormal thermal nociception (MGI Ref ID J:106368)

41% increase in foot withdrawal latency from painful thermal stimuli

100% slower tail withdrawal latency

endocrine/exocrine gland phenotype

abnormal adrenal gland morphology (MGI Ref ID J:60585)

abnormal adrenal cortex morphology (MGI Ref ID J:60585)

increased lipid droplets seen at six months

abnormal adrenal medulla morphology (MGI Ref ID J:60585)

increased lipid droplets seen at six months

abnormal gland physiology (MGI Ref ID J:60585)

hypersecretion of corticosterone (MGI Ref ID J:60585)

fter 10 min of restraint stress plasma levels are elevated at six months but not at three months

elevated adrenal levels at six months but not earlier

hypopituitarism (MGI Ref ID J:60585)

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

adipose tissue phenotype

decreased brown adipose tissue amount (MGI Ref ID J:60585)

decreased interscapular brown fat at 18 but not at 6 months

decreased white adipose tissue amount (MGI Ref ID J:60585)

epididymal white fat reduced at both 6 and 18 months

Apoe^tm1Unc/Apoe^tm1Unc
B6.Cg-Apoe^tm1Unc Fas^lpr
immune system phenotype

increased anti-nuclear antigen antibody level (MGI Ref ID J:133606)

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

increased anti-double stranded DNA antibody level (MGI Ref ID J:133606)

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

increased immunoglobulin level (MGI Ref ID J:133606)

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

increased susceptibility to systemic lupus erythematosus (MGI Ref ID J:133606)

homeostasis/metabolism phenotype

increased circulating cholesterol level (MGI Ref ID J:133606)

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

cardiovascular system phenotype

increased susceptibility to atherosclerosis (MGI Ref ID J:133606)

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

The following phenotype information may relate to a genetic background differing from this JAX^® Mice strain.
Apoe^tm1Unc/Apoe^tm1Unc
either: 129P2/OlaHsd-Apoe^tm1Unc or (involves: 129P2/OlaHsd * C57BL/6J)
cardiovascular system phenotype

atherosclerotic lesions (MGI Ref ID J:43846)

homeostasis/metabolism phenotype

xanthoma (MGI Ref ID J:43846)

3 of 15 aged mice (17 months) fed conventional chow exhibit small choroidal xanthomas

aged mice (15 - 23 months) kept on a high fat/high cholesterol diet from age 17 weeks exhibit cerebral xanthomatous lesions, consisting of crystalline cholesterol clefts, lipid globules and foam cells

Apoe^tm1Unc/Apoe^tm1Unc
involves: 129P2/OlaHsd * C57BL/6
cardiovascular system phenotype

abnormal PGE2 physiology (MGI Ref ID J:125376)

amount of PGE2 in aortas is 4X higher than in controls

PGE2 level doubles on a high fat diet

atherosclerotic lesions (MGI Ref ID J:80689)

greater than in wild-type

homeostasis/metabolism phenotype

hyperlipidemia (MGI Ref ID J:80689)

relative to wild-type

increased circulating cholesterol level (MGI Ref ID J:80689)

relative to wild-type

increased circulating triglyceride level (MGI Ref ID J:80689)

relative to wild-type

nervous system phenotype

abnormal glial cell physiology (MGI Ref ID J:58019)

astrocytes secrete less phospholipids or free cholesterol compared to wild type astrocytes

Apoe^tm1Unc/Apoe^tm1Unc
involves: 129P2/OlaHsd
behavior/neurological phenotype

increased anxiety-related response (MGI Ref ID J:101973)

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 (MGI Ref ID J:101973)

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

hearing/vestibular/ear phenotype

increased startle reflex (MGI Ref ID J:101973)

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

homeostasis/metabolism phenotype

decreased cerebral infarction size (MGI Ref ID J:133156)

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

increased circulating corticosterone level (MGI Ref ID J:101973)

all males have higher plasma concentrations than wild-type after behavioral testing

nervous system phenotype

abnormal dendrite morphology (MGI Ref ID J:101973)

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

decreased cerebral infarction size (MGI Ref ID J:133156)

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

cardiovascular system phenotype

increased susceptibility to atherosclerosis (MGI Ref ID J:107390)

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

Apoe^tm1Unc/Apoe^tm1Unc
involves: 129P2/OlaHsd * 129S4/SvJae * C57BL/6
cardiovascular system phenotype

atherosclerotic lesions (MGI Ref ID J:66419)

most severe in the aortic arch region

Gene & Allele Details

Allele Symbol		Apoe^tm1Unc
Allele Name		targeted mutation 1, University of North Carolina
Common Name(s)		APOE KO; AopE(-); ApoE-KO; Apoe^tm1Un; apoE-; apoE0; epsilon-;
Mutation Made By		Nobuyo Maeda, Univ of North Carolina at Chapel Hill
Strain of Origin		129P2/OlaHsd
ES Cell Line Name		E14TG2a
ES Cell Line Strain		129P2/OlaHsd
Gene Symbol and Name		Apoe, apolipoprotein E
Chromosome		7
Gene Common Name(s)		AD2; AI255918; LPG; MGC1571; apoprotein; expressed sequence AI255918;
General Note		In Apoe^tm1Unc mutant mice also carrying Csf1^op, atherotic lesions of the proximal aorta were abolished or significantly reduced in size relative to Apoe mutants homozygous for the normal allele at Csf1 (J:40136). The results may have been due to reduced macrophages or M-CSF, but were not due to reductions in circulating lipoprotein (J:40136).
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. [MGI Ref ID J:1050]

Control Information

Allele	Control
Apoe^tm1Unc	000664 C57BL/6J

Considerations for Choosing Controls

Genotyping Protocols

Apoe^tm1Unc

Colony Maintenance

Diet Information	JAX West and Bar Harbor Diets

Related Strains

Strains carrying Apoe^tm1Unc allele

002246 B6.129-Apoe^tm1Unc Ldlr^tm1Her/J

007224 B6.Cg-Apoe^tm1Unc(D12Mit182-D12Mit2)/Pgn

004632 B6.Cg-Tg(GFAP-APOE*2)14Hol Apoe^tm1Unc/J

004633 B6.Cg-Tg(GFAP-APOE*3)37Hol Apoe^tm1Unc/J

004631 B6.Cg-Tg(GFAP-APOE*4)1Hol Apoe^tm1Unc/J

002878 B6;129-Apob^tm1Sgy Apoe^tm1Unc/J

002879 B6;129-Apob^tm2Sgy Apoe^tm1Unc/J

002245 B6;129-Apoe^tm1Unc Ldlr^tm1Her/J

004362 B6;129-Scarb1^tm1Kri Apoe^tm1Unc/J

View Strains carrying Apoe^tm1Unc (9 strains)

Phenotypic Data

Body Weight Information - JAX^® Mice Strain B6.129P2-Apoe^tm1Unc/J (002052)
(This chart reflects the typical correlation between body weight and age for mice maintained in production colonies at The Jackson Laboratory.)
Mouse Phenome Database
JAX^® Physiological Data Summary [pdf]
JAX^® Physiological Data Protocol [pdf]

Additional Web Information

Congenic Nomenclature
Genetic Quality Control Annual Report
JAX^® NOTES, Fall 2003; 491. JAX West Expansion
JAX^® Physiological Data Protocol [pdf]
JAX^® Physiological Data Summary [pdf]
Visit the Alzheimer's Disease Mouse Model Resource site for helpful information on Alzheimer's Disease and research resources.

Animal Health Reports

Room Number AX1
Room Number AX3
Room Number MP14
Room Number MP15
Room Number RB08

Research Applications

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

Diabetes and Obesity Research
Obesity Without Diabetes (diet-induced)

Neurobiology Research
Alzheimer's Disease (APOE mutants)
Behavioral and Learning Defects
Neurodegeneration

Apoe^tm1Unc related

Cardiovascular Research
Atherosclerosis
Hypercholesterolemia

Mouse/Human Gene Homologs
Alzheimer's
hyperlipoproteinemia, type III

References

Selected Reference(s)

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):4471-5. [PubMed: 1584779] [MGI Ref ID J:1050]

Additional References

Price and Supply Information

Strain Name:	*B6.129P2-Apoe^tm1Unc/J*
Stock Number:	002052

Price Details

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Supply Details

Standard Supply	JAX Ready Strain^® (Level 1). Most popular strains. Readily available in any quantity you need.
Supply Notes	Shipped at a specific age in weeks. Mice at a precise age in days, littermates and retired breeders are also available. Strains that must be genotyped are not available until five to seven weeks of age. This strain is available from some international Charles River Laboratories (CRL) breeding facilities in Japan and/or Europe. For more information, see the Worldwide Distributor List for JAX^® Mice. This strain is included in the Induced Mutant Resource Colony collection. Genomic DNA is available for this strain from the Mouse DNA Resource.
Licensing	See General Terms and Conditions below
Control Information	View Control Information in Strain Details.

General Terms and Conditions

View JAX^® Mice & Services Conditions of Use.

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.

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002246	B6.129-Apoe^tm1Unc Ldlr^tm1Her/J
007224	B6.Cg-Apoe^tm1Unc(D12Mit182-D12Mit2)/Pgn
004632	B6.Cg-Tg(GFAP-APOE2)14Hol Apoe^tm1Unc*/J
004633	B6.Cg-Tg(GFAP-APOE3)37Hol Apoe^tm1Unc*/J
004631	B6.Cg-Tg(GFAP-APOE4)1Hol Apoe^tm1Unc*/J
002878	B6;129-Apob^tm1Sgy Apoe^tm1Unc/J
002879	B6;129-Apob^tm2Sgy Apoe^tm1Unc/J
002245	B6;129-Apoe^tm1Unc Ldlr^tm1Her/J
004362	B6;129-Scarb1^tm1Kri Apoe^tm1Unc/J

Strain Name:

B6.129P2-Apoetm1Unc/J

Stock Number:

002052

Availability:

Level 1

General Terms and Conditions

Product Information

Strain Details

Apoetm1Unc/Apoetm1Unc

Apoetm1Unc/Apoetm1Unc

Apoetm1Unc/Apoetm1Unc

Apoetm1Unc/Apoetm1Unc

Apoetm1Unc/Apoetm1Unc

Apoetm1Unc/Apoetm1Unc

Apoetm1Unc/Apoetm1Unc

Apoetm1Unc/Apoetm1Unc

Gene & Allele Details

Control Information

Genotyping Protocols

Colony Maintenance

Related Strains

Phenotypic Data

Additional Web Information

Animal Health Reports

Research Applications

References

Price and Supply Information

Price Details

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Supply Details

General Terms and Conditions

The Jackson Laboratory's Genotype Promise

B6.129P2-Apoe^tm1Unc/J

Apoe^tm1Unc/Apoe^tm1Unc

Apoe^tm1Unc/Apoe^tm1Unc

Apoe^tm1Unc/Apoe^tm1Unc

Apoe^tm1Unc/Apoe^tm1Unc

Apoe^tm1Unc/Apoe^tm1Unc

Apoe^tm1Unc/Apoe^tm1Unc

Apoe^tm1Unc/Apoe^tm1Unc

Apoe^tm1Unc/Apoe^tm1Unc