Phenotypes for Tg(APPswe,PSEN1dE9)85Dbo MGI:5008418 MGI Mouse

premature death ( J:160557 , J:360724 )

• about 40% of mice are lost by 12 months of age (J:160557)

• mice exhibit reduced lifespan, with survival rate beginning to decline at approximately 8 weeks of age and only approximately 40% of mice survive to 45 weeks (J:360724)

impaired passive avoidance behavior ( J:160557 , J:360724 )

• mice exhibit reduced retention times in the passive avoidance test, indicating reduced memory, however acquisition times are not affected (J:360724)

• mice treated with an anti-FAM195A antibody at 8 months of age show improved memory retention in the passive avoidance test (J:360724)

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

impaired spatial working memory ( J:360724 )

• mice exhibit reduced spontaneous alternation in the Y-maze

• mice administered an anti-FAM19A5 antibody intravenously at 8 months of age show increased spontaneous alternation and thus improved performance in the Y-maze test

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

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

astrocytosis ( J:160557 )

amyloid beta deposits ( J:160557 , J:172426 , J:208080 , J:227541 , J:360724 )

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

• mice develop amyloid beta plaques in the cortex and hippocampus (J:360724)

• mice administered an anti-FAM19A5 antibody intravenously at 8 months of age show a trend toward decreased amyloid beta oligomer and plaque levels that does not reach significance (J:360724)

• 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)

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 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