Description

Strain Information

Type Congenic; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered Mutant Mice. Species laboratory mouse

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.

In an attempt to offer alleles on well-characterized or multiple genetic backgrounds, alleles are frequently moved to a genetic background different from that on which an allele was first characterized. This is the case for the strain above. It should be noted that the phenotype could vary from that originally described. We will modify the strain description if necessary as published results become available.

Development
A targeting vector containing neomycin cassette was used to disrupt exon 3 of the targeted gene. The plasmid used is designated as pNMC109 and the founder line is T-89 in the primary reference. The construct was electroporated into 129P2/OlaHsd-derived E14Tg2a embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6J blastocysts. The resulting chimeric animals were crossed to C57BL/6J mice, and then backcrossed to C57BL/6J for 12 generations. These B6.129P2-Apoe^tm1Unc/J (Stock no. 2052) mice were then backcrossed to AKR/J (Stock no. 648) using a speed congenic protocol to produce this strain.

Related Strains

Strains carrying   Apoe^tm1Unc allele

002246	B6.129-Apoetm1Unc Ldlrtm1Her/J
002052	B6.129P2-Apoetm1Unc/J
007224	B6.Cg-Apoetm1Unc(D12Mit182-D12Mit2)/Pgn
004632	B6.Cg-Tg(GFAP-APOE*2)14Hol Apoetm1Unc/J
004633	B6.Cg-Tg(GFAP-APOE*3)37Hol Apoetm1Unc/J
004631	B6.Cg-Tg(GFAP-APOE*4)1Hol Apoetm1Unc/J
002878	B6;129-Apobtm1Sgy Apoetm1Unc/J
002879	B6;129-Apobtm2Sgy Apoetm1Unc/J
002245	B6;129-Apoetm1Unc Ldlrtm1Her/J
004362	B6;129-Scarb1tm1Kri Apoetm1Unc/J
007067	D2.129P2(B6)-Apoetm1Unc/J

View Strains carrying   Apoe^tm1Unc     (11 strains)

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms

      assigned by genotype

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

        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 ± 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
  • 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
  • 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 ± 14.5 cm/s vs 379 ± 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 ± 7.1 vs. 151 ± 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 ± 0.9 vs. 44.5 ± 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 ± 1.1% vs 46.6 ± 0.4%; in contrast, systolic blood pressures remain unaffected (140 ± 7.6 mmHg vs 136 ± 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
• 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

        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

        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

        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

        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
• increased circulating cholesterol level (MGI Ref ID J:61287)
  • 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)
• 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
• hypopituitarism (MGI Ref ID J:60585)
  • restraint stress at 6 months results in disproportionately low ACTH levels as compared to plasma corticosterone levels
• 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
• cardiovascular system phenotype
• atherosclerotic lesions (MGI Ref ID J:61287)
  • 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

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

View Research Applications

Research Applications

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

Cardiovascular Research
Atherosclerosis

Metabolism Research
Lipid Metabolism

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

Genes & Alleles

Gene & Allele Information

Genotyping

Genotyping Information

Genotyping Protocols

Apoe^tm1Unc, HRM, vers. 2
Apoe^tm1Unc, STD PCR, vers. 1

Helpful Links

Optimizing PCR Protocols

References

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

Apoe^tm1Unc related

't Hoen PA; Van der Lans CA; Van Eck M; Bijsterbosch MK; Van Berkel TJ; Twisk J. 2003. Aorta of ApoE-deficient mice responds to atherogenic stimuli by a prelesional increase and subsequent decrease in the expression of antioxidant enzymes. Circ Res 93(3):262-9. [PubMed: 12829615]  [MGI Ref ID J:115676]

Accad M; Smith SJ; Newland DL; Sanan DA; King LE Jr; Linton MF; Fazio S; Farese RV Jr. 2000. Massive xanthomatosis and altered composition of atherosclerotic lesions in hyperlipidemic mice lacking acyl CoA:cholesterol acyltransferase 1 [see comments] J Clin Invest 105(6):711-9. [PubMed: 10727439]  [MGI Ref ID J:61147]

Agrawal S; Febbraio M; Podrez E; Cathcart MK; Stark GR; Chisolm GM. 2007. Signal transducer and activator of transcription 1 is required for optimal foam cell formation and atherosclerotic lesion development. Circulation 115(23):2939-47. [PubMed: 17533179]  [MGI Ref ID J:137115]

Aihara K; Azuma H; Akaike M; Ikeda Y; Sata M; Takamori N; Yagi S; Iwase T; Sumitomo Y; Kawano H; Yamada T; Fukuda T; Matsumoto T; Sekine K; Sato T; Nakamichi Y; Yamamoto Y; Yoshimura K; Watanabe T; Nakamura T; Oomizu A; Tsukada M; Hayashi H; Sudo T; KatoS; Matsumoto T. 2007. Strain-dependent embryonic lethality and exaggerated vascular remodeling in heparin cofactor II-deficient mice. J Clin Invest 117(6):1514-26. [PubMed: 17549254]  [MGI Ref ID J:122173]

Aikawa E; Nahrendorf M; Sosnovik D; Lok VM; Jaffer FA; Aikawa M; Weissleder R. 2007. Multimodality molecular imaging identifies proteolytic and osteogenic activities in early aortic valve disease. Circulation 115(3):377-86. [PubMed: 17224478]  [MGI Ref ID J:130156]

Alexander MR; Knowles JW; Nishikimi T; Maeda N. 2003. Increased atherosclerosis and smooth muscle cell hypertrophy in natriuretic peptide receptor A-/-apolipoprotein E-/- mice. Arterioscler Thromb Vasc Biol 23(6):1077-82. [PubMed: 12702516]  [MGI Ref ID J:103054]

Ali K; Middleton M; Pure E; Rader DJ. 2005. Apolipoprotein E suppresses the type I inflammatory response in vivo. Circ Res 97(9):922-7. [PubMed: 16179587]  [MGI Ref ID J:114634]

Alp NJ; McAteer MA; Khoo J; Choudhury RP; Channon KM. 2004. Increased endothelial tetrahydrobiopterin synthesis by targeted transgenic GTP-cyclohydrolase I overexpression reduces endothelial dysfunction and atherosclerosis in ApoE-knockout mice. Arterioscler Thromb Vasc Biol 24(3):445-50. [PubMed: 14707037]  [MGI Ref ID J:102062]

Amigo L; Quinones V; Mardones P; Zanlungo S; Miquel JF; Nervi F; Rigotti A. 2000. Impaired biliary cholesterol secretion and decreased gallstone formation in apolipoprotein E-deficient mice fed a high-cholesterol diet. Gastroenterology 118(4):772-9. [PubMed: 10734029]  [MGI Ref ID J:107676]

Anderson DR; Tsutsui JM; Xie F; Radio SJ; Porter TR. 2007. The role of complement in the adherence of microbubbles to dysfunctional arterial endothelium and atherosclerotic plaque. Cardiovasc Res 73(3):597-606. [PubMed: 17196951]  [MGI Ref ID J:119533]

Anderson R; Barnes JC; Bliss TV; Cain DP; Cambon K; Davies HA; Errington ML; Fellows LA; Gray RA; Hoh T; Stewart M; Large CH; Higgins GA. 1998. Behavioural, physiological and morphological analysis of a line of apolipoprotein E knockout mouse. Neuroscience 85(1):93-110. [PubMed: 9607706]  [MGI Ref ID J:118390]

Anderson R; Higgins GA. 1997. Absence of central cholinergic deficits in ApoE knockout mice. Psychopharmacology (Berl) 132(2):135-44. [PubMed: 9266610]  [MGI Ref ID J:127860]

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):1216-23. [PubMed: 12671033]  [MGI Ref ID J:84022]

Angeli V; Llodra J; Rong JX; Satoh K; Ishii S; Shimizu T; Fisher EA; Randolph GJ. 2004. Dyslipidemia associated with atherosclerotic disease systemically alters dendritic cell mobilization. Immunity 21(4):561-74. [PubMed: 15485633]  [MGI Ref ID J:93917]

Aprahamian T; Bonegio R; Rizzo J; Perlman H; Lefer DJ; Rifkin IR; Walsh K. 2006. Simvastatin treatment ameliorates autoimmune disease associated with accelerated atherosclerosis in a murine lupus model. J Immunol 177(5):3028-34. [PubMed: 16920939]  [MGI Ref ID J:139547]

Aprahamian T; Rifkin I; Bonegio R; Hugel B; Freyssinet JM; Sato K; Castellot JJ Jr; Walsh K. 2004. Impaired Clearance of Apoptotic Cells Promotes Synergy between Atherogenesis and Autoimmune Disease. J Exp Med 199(8):1121-31. [PubMed: 15096538]  [MGI Ref ID J:91058]

Atkinson RD; Coenen KR; Plummer MR; Gruen ML; Hasty AH. 2008. Macrophage-derived apolipoprotein E ameliorates dyslipidemia and atherosclerosis in obese apolipoprotein E-deficient mice. Am J Physiol Endocrinol Metab 294(2):E284-90. [PubMed: 18029445]  [MGI Ref ID J:133332]

Auger A; Truong TQ; Rhainds D; Lapointe J; Letarte F; Brissette L. 2001. Low and high density lipoprotein metabolism in primary cultures of hepatic cells from normal and apolipoprotein E knockout mice. Eur J Biochem 268(8):2322-30. [PubMed: 11298750]  [MGI Ref ID J:115588]

Babaev VR; Ding L; Reese J; Morrow JD; Breyer MD; Dey SK; Fazio S; Linton MF. 2006. Cyclooxygenase-1 deficiency in bone marrow cells increases early atherosclerosis in apolipoprotein E- and low-density lipoprotein receptor-null mice. Circulation 113(1):108-17. [PubMed: 16380543]  [MGI Ref ID J:121507]

Baldan A; Pei L; Lee R; Tarr P; Tangirala RK; Weinstein MM; Frank J; Li AC; Tontonoz P; Edwards PA. 2006. Impaired development of atherosclerosis in hyperlipidemic Ldlr-/- and ApoE-/- mice transplanted with Abcg1-/- bone marrow. Arterioscler Thromb Vasc Biol 26(10):2301-7. [PubMed: 16888235]  [MGI Ref ID J:128048]

Bales KR; Verina T; Cummins DJ; Du Y; Dodel RC; Saura J; Fishman CE; DeLong CA; Piccardo P; Petegnief V; Ghetti B; Paul SM. 1999. Apolipoprotein E is essential for amyloid deposition in the APP(V717F) transgenic mouse model of Alzheimer's disease. Proc Natl Acad Sci U S A 96(26):15233-8. [PubMed: 10611368]  [MGI Ref ID J:59078]

Bales KR; Verina T; Dodel RC; Du Y; Altstiel L; Bender M; Hyslop P; Johnstone EM; Little SP; Cummins DJ; Piccardo P; Ghetti B; Paul SM. 1997. Lack of apolipoprotein E dramatically reduces amyloid beta-peptide deposition [letter] [see comments] Nat Genet 17(3):263-4. [PubMed: 9354781]  [MGI Ref ID J:43845]

Barile GR; Pachydaki SI; Tari SR; Lee SE; Donmoyer CM; Ma W; Rong LL; Buciarelli LG; Wendt T; Horig H; Hudson BI; Qu W; Weinberg AD; Yan SF; Schmidt AM. 2005. The RAGE axis in early diabetic retinopathy. Invest Ophthalmol Vis Sci 46(8):2916-24. [PubMed: 16043866]  [MGI Ref ID J:103714]

Barlic J; Murphy PM. 2007. Chemokine regulation of atherosclerosis. J Leukoc Biol 82(2):226-36. [PubMed: 17329566]  [MGI Ref ID J:123530]

Barry-Lane PA; Patterson C; van der Merwe M; Hu Z; Holland SM; Yeh ET; Runge MS. 2001. p47phox is required for atherosclerotic lesion progression in ApoE(-/-) mice. J Clin Invest 108(10):1513-22. [PubMed: 11714743]  [MGI Ref ID J:111638]

Barton M; Haudenschild CC; d'Uscio LV; Shaw S; Munter K; Luscher TF. 1998. Endothelin ETA receptor blockade restores NO-mediated endothelial function and inhibits atherosclerosis in apolipoprotein E-deficient mice. Proc Natl Acad Sci U S A 95(24):14367-72. [PubMed: 9826706]  [MGI Ref ID J:51282]

Bates KA; Fonte J; Robertson TA; Martins RN; Harvey AR. 2002. Chronic gliosis triggers Alzheimer's disease-like processing of amyloid precursor protein. Neuroscience 113(4):785-96. [PubMed: 12182886]  [MGI Ref ID J:120711]

Baumgartl J; Baudler S; Scherner M; Babaev V; Makowski L; Suttles J; McDuffie M; Tobe K; Kadowaki T; Fazio S; Kahn CR; Hotamisligil GS; Krone W; Linton M; Bruning JC. 2006. Myeloid lineage cell-restricted insulin resistance protects apolipoproteinE-deficient mice against atherosclerosis. Cell Metab 3(4):247-56. [PubMed: 16581002]  [MGI Ref ID J:129654]

Bechtholt AJ; Smith R; Raber J; Cunningham CL. 2004. Enhanced ethanol-, but not cocaine-induced, conditioned place preference in Apoe(-/-) mice. Pharmacol Biochem Behav 77(4):783-92. [PubMed: 15099924]  [MGI Ref ID J:102259]

Beckers L; Heeneman S; Wang L; Burkly L; Rousch M; Davidson N; Gijbels M; de Winther M; Daemen M; Lutgens E. 2007. Disruption of hedgehog signalling in ApoE - /- mice reduces plasma lipid levels, but increases atherosclerosis due to enhanced lipid uptake by macrophages. J Pathol 212(4):420-8. [PubMed: 17573667]  [MGI Ref ID J:122864]

Bengtsson E; To F; Hakansson K; Grubb A; Branen L; Nilsson J; Jovinge S. 2005. Lack of the cysteine protease inhibitor cystatin C promotes atherosclerosis in apolipoprotein E-deficient mice. Arterioscler Thromb Vasc Biol 25(10):2151-6. [PubMed: 16051881]  [MGI Ref ID J:114346]

Bennett BJ; Scatena M; Kirk EA; Rattazzi M; Varon RM; Averill M; Schwartz SM; Giachelli CM; Rosenfeld ME. 2006. Osteoprotegerin inactivation accelerates advanced atherosclerotic lesion progression and calcification in older ApoE-/- mice. Arterioscler Thromb Vasc Biol 26(9):2117-24. [PubMed: 16840715]  [MGI Ref ID J:128053]

Berbee JF; van der Hoogt CC; Sundararaman D; Havekes LM; Rensen PC. 2005. Severe hypertriglyceridemia in human APOC1 transgenic mice is caused by apoC-I-induced inhibition of LPL. J Lipid Res 46(2):297-306. [PubMed: 15576844]  [MGI Ref ID J:96691]

Bernhagen J; Krohn R; Lue H; Gregory JL; Zernecke A; Koenen RR; Dewor M; Georgiev I; Schober A; Leng L; Kooistra T; Fingerle-Rowson G; Ghezzi P; Kleemann R; McColl SR; Bucala R; Hickey MJ; Weber C. 2007. MIF is a noncognate ligand of CXC chemokine receptors in inflammatory and atherogenic cell recruitment. Nat Med 13(5):587-596. [PubMed: 17435771]  [MGI Ref ID J:121807]

Bhattacharjee PS; Neumann DM; Stark D; Thompson HW; Hill JM. 2006. Apolipoprotein E modulates establishment of HSV-1 latency and survival in a mouse ocular model. Curr Eye Res 31(9):703-8. [PubMed: 16966142]  [MGI Ref ID J:119878]

Biswas SK; Newby DE; Rahman I; Megson IL. 2005. Depressed glutathione synthesis precedes oxidative stress and atherogenesis in Apo-E(-/-) mice. Biochem Biophys Res Commun 338(3):1368-73. [PubMed: 16263083]  [MGI Ref ID J:103465]

Bjorkbacka H; Kunjathoor VV; Moore KJ; Koehn S; Ordija CM; Lee MA; Means T; Halmen K; Luster AD; Golenbock DT; Freeman MW. 2004. Reduced atherosclerosis in MyD88-null mice links elevated serum cholesterol levels to activation of innate immunity signaling pathways. Nat Med 10(4):416-21. [PubMed: 15034566]  [MGI Ref ID J:90091]

Blasiole DA; Oler AT; Attie AD. 2008. Regulation of ApoB secretion by the low density lipoprotein receptor requires exit from the endoplasmic reticulum and interaction with ApoE or ApoB. J Biol Chem 283(17):11374-81. [PubMed: 18272520]  [MGI Ref ID J:136523]

Bobkova D; Honsova E; Kovar J; Poledne R. 2004. Effect of diets on lipoprotein concentrations in heterozygous apolipoprotein E-deficient mice. Physiol Res 53(6):635-43. [PubMed: 15588132]  [MGI Ref ID J:102284]

Bobryshev YV; Babaev VR; Lord RS; Watanabe T. 1999. Ultrastructural identification of cells with dendritic cell appearance in atherosclerotic aorta of apolipoprotein E deficient mice J Submicrosc Cytol Pathol 31(4):527-31. [PubMed: 10685393]  [MGI Ref ID J:60456]

Bodary PF; Shen Y; Vargas FB; Bi X; Ostenso KA; Gu S; Shayman JA; Eitzman DT. 2005. Alpha-galactosidase A deficiency accelerates atherosclerosis in mice with apolipoprotein E deficiency Circulation 111(5):629-32. [PubMed: 15668341]  [MGI Ref ID J:108541]

Boesten LS; Zadelaar AS; van Nieuwkoop A; Hu L; Jonkers J; van de Water B; Gijbels MJ; van der Made I; de Winther MP; Havekes LM; van Vlijmen BJ. 2006. Macrophage retinoblastoma deficiency leads to enhanced atherosclerosis development in ApoE-deficient mice. FASEB J 20(7):953-5. [PubMed: 16585057]  [MGI Ref ID J:111494]

Boisvert WA; Black AS; Curtiss LK. 1999. ApoA1 reduces free cholesterol accumulation in atherosclerotic lesions of ApoE-deficient mice transplanted with ApoE-expressing macrophages. Arterioscler Thromb Vasc Biol 19(3):525-30. [PubMed: 10073953]  [MGI Ref ID J:55595]

Boord JB; Maeda K; Makowski L; Babaev VR; Fazio S; Linton MF; Hotamisligil GS. 2002. Adipocyte fatty acid-binding protein, aP2, alters late atherosclerotic lesion formation in severe hypercholesterolemia. Arterioscler Thromb Vasc Biol 22(10):1686-91. [PubMed: 12377750]  [MGI Ref ID J:103224]

Boord JB; Maeda K; Makowski L; Babaev VR; Fazio S; Linton MF; Hotamisligil GS. 2004. Combined adipocyte-macrophage fatty acid-binding protein deficiency improves metabolism, atherosclerosis, and survival in apolipoprotein E-deficient mice. Circulation 110(11):1492-8. [PubMed: 15353487]  [MGI Ref ID J:102223]

Boring L; Gosling J; Cleary M; Charo IF. 1998. Decreased lesion formation in CCR2-/- mice reveals a role for chemokines in the initiation of atherosclerosis. Nature 394(6696):894-7. [PubMed: 9732872]  [MGI Ref ID J:111471]

Bour A; Grootendorst J; Vogel E; Kelche C; Dodart JC; Bales K; Moreau PH; Sullivan PM; Mathis C. 2008. Middle-aged human apoE4 targeted-replacement mice show retention deficits on a wide range of spatial memory tasks. Behav Brain Res 193(2):174-82. [PubMed: 18572260]  [MGI Ref ID J:139186]

Bourdillon MC; Poston RN; Covacho C; Chignier E; Bricca G; McGregor JL. 2000. ICAM-1 deficiency reduces atherosclerotic lesions in double-knockout mice (ApoE(-/-)/ICAM-1(-/-)) fed a fat or a chow diet. Arterioscler Thromb Vasc Biol 20(12):2630-5. [PubMed: 11116064]  [MGI Ref ID J:103384]

Bradley MN; Hong C; Chen M; Joseph SB; Wilpitz DC; Wang X; Lusis AJ; Collins A; Hseuh WA; Collins JL; Tangirala RK; Tontonoz P. 2007. Ligand activation of LXR beta reverses atherosclerosis and cellular cholesterol overload in mice lacking LXR alpha and apoE. J Clin Invest 117(8):2337-46. [PubMed: 17657314]  [MGI Ref ID J:123957]

Branen L; Hovgaard L; Nitulescu M; Bengtsson E; Nilsson J; Jovinge S. 2004. Inhibition of tumor necrosis factor-alpha reduces atherosclerosis in apolipoprotein E knockout mice. Arterioscler Thromb Vasc Biol 24(11):2137-42. [PubMed: 15345516]  [MGI Ref ID J:103699]

Braunersreuther V; Zernecke A; Arnaud C; Liehn EA; Steffens S; Shagdarsuren E; Bidzhekov K; Burger F; Pelli G; Luckow B; Mach F; Weber C. 2007. Ccr5 but not Ccr1 deficiency reduces development of diet-induced atherosclerosis in mice. Arterioscler Thromb Vasc Biol 27(2):373-9. [PubMed: 17138939]  [MGI Ref ID J:128063]

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):2527-34. [PubMed: 15014128]  [MGI Ref ID J:90126]

Bro S; Borup R; Andersen CB; Moeller F; Olgaard K; Nielsen LB. 2006. Uremia-specific effects in the arterial media during development of uremic atherosclerosis in apolipoprotein E-deficient mice. Arterioscler Thromb Vasc Biol 26(3):570-5. [PubMed: 16373611]  [MGI Ref ID J:127966]

Broedl UC; Maugeais C; Millar JS; Jin W; Moore RE; Fuki IV; Marchadier D; Glick JM; Rader DJ. 2004. Endothelial lipase promotes the catabolism of ApoB-containing lipoproteins. Circ Res 94(12):1554-61. [PubMed: 15117821]  [MGI Ref ID J:100064]

Brown MD; Jin L; Jien ML; Matsumoto AH; Helm GA; Lusis AJ; Frank JS; Shi W. 2004. Lipid retention in the arterial wall of two mouse strains with different atherosclerosis susceptibility. J Lipid Res 45(6):1155-61. [PubMed: 15105414]  [MGI Ref ID J:89769]

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):1318-31. [PubMed: 14597759]  [MGI Ref ID J:86531]

Burgos JS; Ramirez C; Sastre I; Alfaro JM; Valdivieso F. 2005. Herpes simplex virus type 1 infection via the bloodstream with apolipoprotein E dependence in the gonads is influenced by gender. J Virol 79(3):1605-12. [PubMed: 15650186]  [MGI Ref ID J:95551]

Burleigh ME; Babaev VR; Oates JA; Harris RC; Gautam S; Riendeau D; Marnett LJ; Morrow JD; Fazio S; Linton MF. 2002. Cyclooxygenase-2 promotes early atherosclerotic lesion formation in LDL receptor-deficient mice. Circulation 105(15):1816-23. [PubMed: 11956125]  [MGI Ref ID J:103220]

Burleigh ME; Babaev VR; Yancey PG; Major AS; McCaleb JL; Oates JA; Morrow JD; Fazio S; Linton MF. 2005. Cyclooxygenase-2 promotes early atherosclerotic lesion formation in ApoE-deficient and C57BL/6 mice. J Mol Cell Cardiol 39(3):443-52. [PubMed: 16040051]  [MGI Ref ID J:103979]

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):226-231. [PubMed: 11120928]  [MGI Ref ID J:66879]

Burton CA; Patel S; Mundt S; Hassing H; Zhang D; Hermanowski-Vosatka A; Wright SD; Chao YS; Detmers PA; Sparrow CP. 2002. Deficiency in sPLA(2) does not affect HDL levels or atherosclerosis in mice. Biochem Biophys Res Commun 294(1):88-94. [PubMed: 12054745]  [MGI Ref ID J:77028]

Buttini M; Orth M; Bellosta S; Akeefe H; Pitas RE; Wyss-Coray T; Mucke L; Mahley RW. 1999. Expression of human apolipoprotein E3 or E4 in the brains of Apoe-/- mice: isoform-specific effects on neurodegeneration. J Neurosci 19(12):4867-80. [PubMed: 10366621]  [MGI Ref ID J:55835]

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