Mouse Genome Informatics
cx1
    Tg(APP)8.9Btla/Tg(APP)8.9Btla
Tg(SOD1)51Yg/Tg(SOD1)51Yg

involves: 129S2/SvPas * BALB/c * C57BL/6J * DBA/2
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
behavior/neurological
• mice spend greater amounts of time in the closed arms of an elevated plus maze than Tg(SOD1)51Yg or Tg(APP)8.9Btla mice; time per entry into dark arms is increased relative to Tg(APP)8.9Btla mice and total entries into dark arms is greater than controls
• mice spend much more time in dark side of dark-light box than either single transgenic line or controls
• 9-month old mice show impaired memory retention in Morris water maze, exhibiting delayed escape latency compared to controls in all 6 trials
• exploratory behavior is increased for both familiar and novel objects
• impairment observed at 10 months of age; mice show greater impairment than Tg(APP)8.9Btla mice
• at 9 months, a delay of learning process in Morris water maze is observed compared to controls; double mutants are significantly impaired relative to controls
• at 4.5 months of age, rate of learning platform position during first day of Morris water maze testing is impaired compared to controls or Tg(APP)8.9Btla/Tg(SOD1)69Yg double mutants
• transgenic mice display more spontaneous locomotor activity than controls

nervous system
• mic show a 2-fold increase of cortical APP proteins and a 2.5-2.8-fold increase in hippocampal APP levels compared to Tg(APP)8.9Btla mice
• no Abeta peptides are detected in 5 month old mice
• LTP is impaired


Mouse Genome Informatics
cx2
    Tg(APP)8.9Btla/Tg(APP)8.9Btla
Tg(SOD1)69Yg/Tg(SOD1)69Yg

involves: 129S2/SvPas * BALB/c * C57BL/6J * DBA/2
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
behavior/neurological
• 9-month old mice show impaired memory retention in Morris water maze, exhibiting delayed escape latency compared to controls in all 6 trials
• impairment observed at 10 months of age in Morris water maze
• at 9 months, a delay of learning process in Morris water maze is observed compared to controls
• at 4.5 months of age, rate of learning platform position during first day of Morris water maze testing is impaired

nervous system
• mice display depotentiation to a smaller EPSP size
• LTP is impaired

other phenotype
• mic show a 1.6-fold increase of cortical APP proteins and a 1.8-2.1-fold increase in hippocampal APP levels compared to Tg(APP)8.9Btla mice


Mouse Genome Informatics
cx3
    Psen1tm1.1Ruvi/Psen1tm1.1Ruvi
Tg(APP)8.9Btla/0

involves: 129S2/SvPas * C57BL/6J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• keratan sulfate-positive-activated microglia
• in the cerebral cortex with amyloid deposition
• scarce small plaques in the hippocampus of young animals becoming more prominent with age
• small and scattered plaques at 6 months in the cerebral cortex
• prominent plaques with age in the neocortex and leptomeninges
• small and moderate sized plaques in the cerebral cortex
• parenchymal amyloid deposition in the cerebellum of older mice
• neuritic dystrophy with clusters of swollen and abnormally distorted neuritic profiles

other phenotype
• scarce small plaques in the hippocampus of young animals becoming more prominent with age
• small and scattered plaques at 6 months in the cerebral cortex
• prominent plaques with age in the neocortex and leptomeninges
• small and moderate sized plaques in the cerebral cortex
• parenchymal amyloid deposition in the cerebellum of older mice

immune system
• keratan sulfate-positive-activated microglia

hematopoietic system
• keratan sulfate-positive-activated microglia


Mouse Genome Informatics
tg4
    Tg(APP)8.9Btla/Tg(APP)8.9Btla
involves: 129S2/SvPas
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
behavior/neurological
• mice spend less time per entry into dark arms than controlsmice spend less time per entry into dark arms than controls
• mice exit dark side of dark-light box more often than controls
• exploratory behavior is increased for both familiar and novel objects
• at 5.5 months of age, mice do not appear to recall platform position from the previous day of training and show a lower learning rate over subsequent trials
• impairment observed at 10 months of age
• at 9 months, a delay of learning process in Morris water maze is observed compared to controls
• transgenic mice display more spontaneous locomotor activity than controls; activity is higher than in Tg(APP)8.9Btla or Tg(SOD1)51Yg mice

vision/eye
N
• little or no perturbation of the retinas structure or cornea is observed (J:80534)
• numerous bodies with circular profiles are present in all lens sections examined
• circles are present in lenses from mice >6 months of age; circles are 1-5 um in diameter
• lenses from 6 and 16 month-old mice contain swollen cortical fiber cells and lens plaques
• fiber cell nuclei are disorganized in the outer cortical region compared to wild-type
• lens degeneration is variable in severity and onset; in some cases, one lens is more severely affected than the other side
• individual fiber cells are irregularly shaped and fiber cell arrays are misaligned
• lens fiber cell membranes are morphologically abnormal
• mice display age-related fiber cell degeneration and cortical plaque formation

nervous system
N
• no Abeta peptides are detected in 5 month old mice (J:96742)

Mouse Models of Human Disease
OMIM IDRef(s)
Alzheimer Disease; AD 104300 J:96742