Phenotypes associated with this allele

• Allele Symbol: Apoe^{tm3(APOE*4)Mae}
• Allele Name: targeted mutation 3, Nobuyo Maeda
• Allele ID: MGI:2158398
• Summary: 5 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Apoe^tm3(APOE*4)Mae/Apoe^tm3(APOE*4)Mae	B6.129P2-Apoe^tm3(APOE*4)Mae	MGI:4355228
hm2	Apoe^tm3(APOE*4)Mae/Apoe^tm3(APOE*4)Mae	involves: 129P2/OlaHsd * C57BL/6	MGI:4355227
cx3	Apoe^tm3(APOE*4)Mae/Apoe^tm3(APOE*4)Mae Ldlr^tm1(LDLR)Mae/Ldlr^+	involves: 129P2/OlaHsd * 129S7/SvEvBrd * C57BL/6	MGI:4355231
cx4	Apoe^tm3(APOE*4)Mae/Apoe^tm3(APOE*4)Mae Tg(Thy1-APPSwDutIowa)BWevn/?	involves: 129P2/OlaHsd * C57BL/6	MGI:4355230
cx5	Apoe^tm3(APOE*4)Mae/Apoe^tm3(APOE*4)Mae Tg(APPSWE)2576Kha/?	involves: 129P2/OlaHsd * C57BL/6 * SJL	MGI:4355229

Genotype
MGI:4355228

hm1

• Allelic Composition: Apoe^{tm3(APOE*4)Mae}/Apoe^{tm3(APOE*4)Mae}
• Genetic Background: B6.129P2-Apoe^{tm3(APOE*4)Mae}

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

behavior/neurological

abnormal spatial reference memory ( J:97643 )

• low retention in water maze tests

• performance improves more with training than for Apoe^{tm2(APOE*3)Mae} mice

• performance in "delayed matching to place" does not improve

abnormal spatial working memory ( J:97643 )

• females are deficient in their ability to recognize spatial changes in object configuration in open field tests

Genotype
MGI:4355227

hm2

• Allelic Composition: Apoe^{tm3(APOE*4)Mae}/Apoe^{tm3(APOE*4)Mae}
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6

growth/size/body

abnormal postnatal growth ( J:151284 )

• weight gain slows down after 4 weeks on high fat diets relative to Apoe^{tm2(APOE*3)Mae}

homeostasis/metabolism

amyloid beta deposits ( J:101147 )

• aged (65-127 weeks) mutants fed a high-fat diet exhibit perivascular amyloid beta immunoreactivity in the eyes indicating amyloid beta deposits

abnormal glucose homeostasis ( J:151284 )

• reduced insulin stimulated glucose uptake by epididymal fat

impaired glucose tolerance ( J:151284 )

• after 2 months on a high fat diet

abnormal lipid level ( J:74417 )

abnormal circulating lipid level ( J:151284 )

• slower clearance of lipid from the blood after ingestion

decreased circulating HDL cholesterol level ( J:74417 )

• relative to Apoe^{tm2(APOE*3)Mae} regardless of diet

increased circulating VLDL cholesterol level ( J:74417 )

• relative to Apoe^{tm2(APOE*3)Mae} regardless of diet

• increased cholesterol/fatty acid ratio on a normal diet relative to Apoe^{tm2(APOE*3)Mae}

• increased diameter of VLDL particles relative to Apoe^{tm2(APOE*3)Mae}

• reduced clearance of Apoe deficient VLDL relative to Apoe^{tm2(APOE*3)Mae}

decreased circulating triglyceride level ( J:74417 )

• in the HDL fraction relative to ApoeApoe^{tm2(APOE*3)Mae} regardless of diet

increased circulating VLDL triglyceride level ( J:74417 )

• relative to Apoe^{tm2(APOE*3)Mae} regardless of diet

cardiovascular system

increased susceptibility to atherosclerosis ( J:74417 )

• lesion size twice that in Apoe^{tm2(APOE*3)Mae} mice after 3 months on an atherogenic diet

retina neovascularization ( J:101147 )

• aged (65-127 weeks) mutants fed a high-fat diet exhibit neovascularization, ranging from mild neovascularization confined to an area adjacent to the RPE and Bruch's membrane to more extensive neovascularization that extends through the RPE and subretinal space and into the neural retina

• some aged miced fed a high-fat diet exhibit extensive neovascular lesions that involve the outer retinal vasculature

adipose tissue

abnormal fat cell morphology ( J:151284 )

• fewer small adipocytes

abnormal epididymal fat pad morphology ( J:151284 )

• less epididymal fat than in Apoe^{tm2(APOE*3)Mae} mice

immune system

increased interleukin-6 secretion ( J:86768 )

• in response to lipopolysaccharide injection, peaking after 3 hours

increased tumor necrosis factor secretion ( J:86768 )

• in response to lipopolysaccharide injection, peaking after 1 hour

abnormal response to infection ( J:138241 )

• higher level of HSV-1 shedding 6 days after ocular infection

• higher numbers of virus in the trigeminal nerve than in controls

vision/eye

retina neovascularization ( J:101147 )

• aged (65-127 weeks) mutants fed a high-fat diet exhibit neovascularization, ranging from mild neovascularization confined to an area adjacent to the RPE and Bruch's membrane to more extensive neovascularization that extends through the RPE and subretinal space and into the neural retina

• some aged miced fed a high-fat diet exhibit extensive neovascular lesions that involve the outer retinal vasculature

abnormal retina pigment epithelium morphology ( J:101147 )

• aged (65-127 weeks) mutants fed a high-fat diet exhibit severe retinal pigment epithelium (RPE) changes, including RPE hyperpigmentation, hypopigmentation and atrophy resulting in a thinner RPE cell layer, thick sub-RPE basal deposits and soft drusenoid deposits rich in neutral lipids

• RPE migration and proliferation are seen in areas of vascular invasion of the retina in aged mutants fed a high-fat diet

• aged mutants fed a high-fat diet exhibit disorganized or absent RPE basal infoldings and accumulation of deposits between the RPE and Bruch's membrane of varying thickness

• mutants that develop neovascularization show capillaries present on the RPE

retina pigment epithelium atrophy ( J:101147 )

• atrophy of the retinal pigment epithelium is seen in aged mutants fed a high-fat diet

cornea opacity ( J:138241 )

• corneal hazing 9 days after ocular infection with HSV-1

• stromal opacity in 70% of mice by day 11

thin retina outer nuclear layer ( J:101147 )

• aged (65-127 weeks) mutants fed a high-fat diet exhibit thinning of the outer nuclear layer

retina degeneration ( J:101147 )

abnormal Bruch membrane morphology ( J:101147 )

• aged (65-127 weeks) mutants fed a high-fat diet exhibit Bruch's membrane thickening

• mutants that develop neovascularization show regions of thinning or loss of Bruch's membrane and capillaries present on choroidal sides of Bruch's membrane

nervous system

amyloid beta deposits ( J:101147 )

• aged (65-127 weeks) mutants fed a high-fat diet exhibit perivascular amyloid beta immunoreactivity in the eyes indicating amyloid beta deposits

pigmentation

abnormal retina pigment epithelium morphology ( J:101147 )

• aged (65-127 weeks) mutants fed a high-fat diet exhibit severe retinal pigment epithelium (RPE) changes, including RPE hyperpigmentation, hypopigmentation and atrophy resulting in a thinner RPE cell layer, thick sub-RPE basal deposits and soft drusenoid deposits rich in neutral lipids

• RPE migration and proliferation are seen in areas of vascular invasion of the retina in aged mutants fed a high-fat diet

• aged mutants fed a high-fat diet exhibit disorganized or absent RPE basal infoldings and accumulation of deposits between the RPE and Bruch's membrane of varying thickness

• mutants that develop neovascularization show capillaries present on the RPE

retina pigment epithelium atrophy ( J:101147 )

• atrophy of the retinal pigment epithelium is seen in aged mutants fed a high-fat diet

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
age related macular degeneration 1		DOID:0110014	OMIM:603075	J:101147

Genotype
MGI:4355231

cx3

• Allelic Composition: Apoe^{tm3(APOE*4)Mae}/Apoe^{tm3(APOE*4)Mae}; Ldlr^tm1(LDLR)Mae/Ldlr⁺
• Genetic Background: involves: 129P2/OlaHsd * 129S7/SvEvBrd * C57BL/6

homeostasis/metabolism

amyloid beta deposits ( J:146721 )

• significant plaque development on a high fat diet relative to Apoe^{tm2(APOE*3)Mae} mice who show very little plaque development

abnormal circulating lipid level ( J:146721 )

• significantly lower lipid levels on a normal fat diet

increased circulating cholesterol level ( J:146721 )

• greater increase in total cholesterol when fed a high fat diet than seen in Apoe^{tm2(APOE*3)Mae} mice

• very high total cholesterol to triglyceride ratio on a high fat diet

• increased number of non-HDL particles

• plasma cholesterol decrease over time relative to mice lacking Ldlr^tm1(LDLR)Mae

increased circulating triglyceride level ( J:146721 )

• higher triglyceride levels in females on a normal fat diet

nervous system

amyloid beta deposits ( J:146721 )

• significant plaque development on a high fat diet relative to Apoe^{tm2(APOE*3)Mae} mice who show very little plaque development

Genotype
MGI:4355230

cx4

• Allelic Composition: Apoe^{tm3(APOE*4)Mae}/Apoe^{tm3(APOE*4)Mae}; Tg(Thy1-APPSwDutIowa)BWevn/?
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6

nervous system

abnormal microglial cell morphology ( J:136318 )

• increased number of neuroreactive microglia in cortex

• decreased number of neuroreactive microglia in thalamic region

amyloid beta deposits ( J:136318 )

• plaque deposition in cortical parenchyma increased 20%

• reduced deposition in cerebral microvasculature

• microglia are tightly associated with parenchymal plaque amyloid

abnormal astrocyte morphology ( J:136318 )

• increased number of neuroreactive astrocytes in cortex

• decreased number of neuroreactive astrocytes in thalamic region

hematopoietic system

abnormal microglial cell morphology ( J:136318 )

• increased number of neuroreactive microglia in cortex

• decreased number of neuroreactive microglia in thalamic region

immune system

abnormal microglial cell morphology ( J:136318 )

• increased number of neuroreactive microglia in cortex

• decreased number of neuroreactive microglia in thalamic region

homeostasis/metabolism

amyloid beta deposits ( J:136318 )

• plaque deposition in cortical parenchyma increased 20%

• reduced deposition in cerebral microvasculature

• microglia are tightly associated with parenchymal plaque amyloid

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Alzheimer's disease		DOID:10652		J:136318

Genotype
MGI:4355229

cx5

• Allelic Composition: Apoe^{tm3(APOE*4)Mae}/Apoe^{tm3(APOE*4)Mae}; Tg(APPSWE)2576Kha/?
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * SJL

nervous system

amyloid beta deposits ( J:98636 )

• increased levels of Amyloid beta 1-40 in cortical extracts at 3 months of age

• increased ratio of Amyloid beta 40:42 in cortical extracts at 3 months of age

• deposition delayed until after 12 months of age

• Amyloid beta deposition starts around 12-15 months of age

• deposition is almost exclusively in cerebral blood vessels with very few parenchymal plaques at 15 months

cerebral amyloid angiopathy ( J:98636 )

• Amyloid beta deposition starts around 12-15 months of age

• deposition is almost exclusively in cerebral blood vessels

abnormal cerebrospinal fluid amyloid beta 40 isoform level ( J:98636 )

• decreased ratio of Amyloid beta 40:42 in cerebrospinal fluid at 3 months of age

abnormal cerebrospinal fluid amyloid beta 42 isoform level ( J:98636 )

• decreased ratio of Amyloid beta 40:42 in cerebrospinal fluid at 3 months of age

homeostasis/metabolism

amyloid beta deposits ( J:98636 )

• increased levels of Amyloid beta 1-40 in cortical extracts at 3 months of age

• increased ratio of Amyloid beta 40:42 in cortical extracts at 3 months of age

• deposition delayed until after 12 months of age

• Amyloid beta deposition starts around 12-15 months of age

• deposition is almost exclusively in cerebral blood vessels with very few parenchymal plaques at 15 months

cerebral amyloid angiopathy ( J:98636 )

• Amyloid beta deposition starts around 12-15 months of age

• deposition is almost exclusively in cerebral blood vessels

abnormal cerebrospinal fluid amyloid beta 40 isoform level ( J:98636 )

• decreased ratio of Amyloid beta 40:42 in cerebrospinal fluid at 3 months of age

abnormal cerebrospinal fluid amyloid beta 42 isoform level ( J:98636 )

• decreased ratio of Amyloid beta 40:42 in cerebrospinal fluid at 3 months of age

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Alzheimer's disease		DOID:10652		J:98636