All Phenotypes Tg(EIF1AX-Aldh2*E487K)101Oht MGI Mouse

Phenotypes associated with this allele

Allelic Composition	Apoe^tm1Unc/Apoe^tm1Unc Tg(EIF1AX-Aldh2E487K)101Oht/Tg(EIF1AX-Aldh2E487K)101Oht
Genetic Background	B6.Cg-Apoe^tm1Unc Tg(EIF1AX-Aldh2*E487K)101Oht

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Apoe^tm1Unc mutation (33 available); any Apoe mutation (158 available)
Tg(EIF1AX-Aldh2*E487K)101Oht mutation (0 available)

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

behavior/neurological

impaired spatial learning ( J:137374 )

• 6 month old mutants are unable to learn the Morris water maze task and the time spent in the target quadrant during probe trials is shorter than in either single mutant

Allelic Composition	Tg(APPSWE)2576Kha/? Tg(EIF1AX-Aldh2*E487K)101Oht/?
Genetic Background	involves: C57BL/6 * SJL

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(APPSWE)2576Kha mutation (5 available)
Tg(EIF1AX-Aldh2*E487K)101Oht mutation (0 available)

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

mortality/aging

premature death ( J:219346 )

• mutants begin dying by 120 days of age and death rate accelerates after 240 days compared to either single mutant

growth/size/body

decreased body weight ( J:219346 )

• mutants weigh less than wild-type mice and single Tg(EIF1AX-Aldh2*E487K)101Oht mice, but exhibit no weight differences from single Tg(APPSWE)2576Kha mice

behavior/neurological

abnormal object recognition memory ( J:219346 )

• in the object recognition test, exploratory preference for the novel object is lower at 3 months of age compared to wild-type mice or either single mutant, and is lower at 6 months of age compared to wild-type mice or single Tg(EIF1AX-Aldh2*E487K)101Oht mice

abnormal spatial working memory ( J:219346 )

• at 3 and 6 months of age, the alternation rate of Y-maze is lower than in wild-type mice or either single mutant

homeostasis/metabolism

amyloid beta deposits ( J:219346 )

• amyloid beta plaques are detected in the brain at 6 months of age, a time when plaques are not seen in single Tg(APPSWE)2576Kha mice

• at 12-15 months of age, more amyloid beta40 and amyloid beta42 plaques are seen than in single Tg(APPSWE)2576Kha mice

nervous system

amyloid beta deposits ( J:219346 )

• amyloid beta plaques are detected in the brain at 6 months of age, a time when plaques are not seen in single Tg(APPSWE)2576Kha mice

• at 12-15 months of age, more amyloid beta40 and amyloid beta42 plaques are seen than in single Tg(APPSWE)2576Kha mice

tau protein deposits ( J:219346 )

• deposition of phosphorylated tau proteins in the brains is increased at 9 months of age compared to single Tg(APPSWE)2576Kha mice

astrocytosis ( J:219346 )

• mutants show a greater number of astrocyte clusters in the CA1 region of the hippocampus and cerebral cortex at 6, 9, and 12 months of age than single Tg(APPSWE)2576Kha mice

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Alzheimer's disease		DOID:10652		J:219346

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

mortality/aging

premature death ( J:137374 )

• median lifespan is 96 weeks compared to 126 weeks for controls, with maximal lifespan at 129 weeks compared to 153 weeks for controls

behavior/neurological

abnormal object recognition memory ( J:137374 )

• aged (11-14 months), but not young (6-8 months) males show impaired visual recognition memory, with mice not approaching or sniffing a novel object more times than the original object as seen in controls and young mice

impaired spatial learning ( J:137374 )

• in the Morris water maze, 1 and 1.5 year old females are able to learn the task but they require 5 days training to reach criterion compared to 3 days in controls and they spend less time in the target quadrant during proble trials

• however, females at 6 months of age have intact spatial learning and memory and no deficits in probe trials in the Morris water maze

integument

abnormal coat/hair pigmentation ( J:137374 )

• some hair decolorization is seen in one year old males

muscle

muscle weakness ( J:137374 )

• one year old males show muscle weakness

nervous system

abnormal hippocampus morphology ( J:137374 )

• increase in hyperphosphorylated tau in the hippocampus of 1 and 1.5 year old mice

hippocampus pyramidal cell degeneration ( J:137374 )

• degeneration and decrease in pyramidal neurons in the CA1 region of the hippocampus

• 20% and 77.8% of mice show neurodegeneration at 1 year and 1.5 years of age, respectively

• neurons are decreased in the in the hilus of the dentate gyrus of aged mice

astrocytosis ( J:137374 )

• increase in activated astrocytes is seen in the hippocampus of old mice, with 60% and 55.6% of mice showing activation of astrocytes at 1 and 1.5 years of age, respectively

pigmentation

abnormal coat/hair pigmentation ( J:137374 )

• some hair decolorization is seen in one year old males

cellular

increased sensitivity to induced cell death ( J:137374 )

• hippocampal neurons from E17 mutants exposed to the toxic aldehyde 4-hydroxy-2-nonenal (HNE) exhibit shorter neurite length and increased apoptosis, indicating increased sensitivity to HNE and decreased ability to detoxify HNE

• cortical neurons from E17 mutants exposed to HNE also exhibit increased sensitivity to HNE, with neurons showing injury and detaching from the dish

oxidative stress ( J:137374 )

• higher accumulation of the toxic aldehyde 4-hydroxy-2-nonenal (HNE) in the brain, indicating inhibited HNE degradation and enhanced accumulation of reactive oxygen species end products

Contributing Projects: Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Models of Human Cancer database (MMHCdb) (formerly Mouse Tumor Biology (MTB)), Gene Ontology (GO)
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