Phenotypes Associated with This Genotype

Genotype
MGI:5008418

• Allelic Composition: Tg(APPswe,PSEN1dE9)85Dbo/0
• Genetic Background: B6.Cg-Tg(APPswe,PSEN1dE9)85Dbo/Mmjax

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

Beta-amyloid plaques in Tg(APPswe,PSEN1dE9)85Dbo/0 mice and neurofibrillary tangles in Mapt^tm1(EGFP)Klt/Mapt^tm1(EGFP)Klt Tg(MAPT)8cPdav/0 mice

mortality/aging

premature death ( J:160557 )

• about 40% of mice are lost by 12 months of age

behavior/neurological

impaired passive avoidance behavior ( J:160557 )

impaired contextual conditioning behavior ( J:234430 )

• mice exhibit decreased freezing to context

• 4 month old mice infused with the specific PTEN inhibitor VO-OHpic into the brain ventricles over a period for 3-4 weeks show improvement in contextual conditioning behavior

• 4 month old mice infused with a cell-permeable PTEN-PDZ peptide over a period of 3-4 weeks into the brain ventricles show improvement in the contextual fear conditioning tests

• however, VO-OHpic treatment does not affect auditory-cued fear conditioning (hippocampal-independent task), exploratory activity or basal freezing behavior

abnormal spatial learning ( J:160557 , J:172426 )

• severely impaired performance in a morris water maze with much longer latencies to reach a hidden platform (J:160557)

• performance in a morris water maze declines between 3 and 12 months of age (J:160557)

• 6 month old mutants exhibit slower visuospatial learning than control mice (J:172426)

• in the visuospatial re-learning test performed at 9, 11, 13, 15, and 18 months of age, mutants exhibit a decrease in the speed of re-learning the task compared to controls (J:172426)

impaired spatial learning ( J:234430 )

• mice exhibit impaired behavior in the novel object location task

• 4 month old mice infused with the specific PTEN inhibitor VO-OHpic into the brain ventricles over a period for 3-4 weeks show improvement in spatial learning tasks

• 4 month old mice infused with a cell-permeable PTEN-PDZ peptide over a period of 3-4 weeks into the brain ventricles show improvement in the novel object-location task

convulsive seizures ( J:227541 )

• Background Sensitivity: premature death early in life eappears to result from convulsive seizures and is much less frequent on the C57BL/6J background than on the DBA/2J background

nervous system

convulsive seizures ( J:227541 )

• Background Sensitivity: premature death early in life eappears to result from convulsive seizures and is much less frequent on the C57BL/6J background than on the DBA/2J background

amyloid beta deposits ( J:160557 , J:172426 , J:208080 , J:227541 )

• Background Sensitivity: there are more ThioS+ plaques in the cortex on the C57BL/6J background than on the DBA/2J background (J:227541)

♀ • at 2 months of age carriers are indistinguishable from C57BL/6J controls, but at 4 months of age very small plaques are found in the cortex, and at 6 months of age plaques are evident in the cortex and hippocampus (J:208080)

astrocytosis ( J:160557 )

axon degeneration ( J:160557 )

• axon degeneration and synapse loss

abnormal CNS synaptic transmission ( J:234430 )

• basal synaptic transmission is lower in hippocampal slices

• VO-OHpic treatment does not rescue the lower basal synaptic transmission

reduced long-term potentiation ( J:234430 )

• semi-chronic treatment with VO-OHpic fully rescues LTP levels in hippocampal slices

taste/olfaction

taste/olfaction phenotype ( J:172426 )

N • mutants do not exhibit Alzheimer's disease-related impairments in olfactory performance in tests based on an operant conditioning procedure and in tests based on a habituation/dishabituation procedure

homeostasis/metabolism

amyloid beta deposits ( J:160557 , J:172426 , J:208080 , J:227541 )

• Background Sensitivity: there are more ThioS+ plaques in the cortex on the C57BL/6J background than on the DBA/2J background (J:227541)

♀ • at 2 months of age carriers are indistinguishable from C57BL/6J controls, but at 4 months of age very small plaques are found in the cortex, and at 6 months of age plaques are evident in the cortex and hippocampus (J:208080)

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Alzheimer's disease		DOID:10652		J:160557 , J:172426 , J:234430