Mouse Genome Informatics
cx1
    Tg(APP695)3Dbo/0
Tg(PSEN1dE9)S9Dbo/0

B6.Cg-Tg(APP695)3Dbo Tg(PSEN1dE9)S9Dbo/Mmjax
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system

homeostasis/metabolism

Mouse Models of Human Disease
OMIM IDRef(s)
Alzheimer Disease 3 607822 J:157228


Mouse Genome Informatics
cx2
    Sorl1tm1Tew/Sorl1tm1Tew
Tg(APP695)3Dbo/0
Tg(PSEN1dE9)S9Dbo/0

involves: 129 * C3H/HeJ * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• amyloid beta levels and amyloid plaque burden are increased at 4.5 and 6 months of age, but not at 12 months of age, compared to transgenic mice wild-type for Sorl1 suggesting an acceleration in accumulation of amyloid beta
• some of the largest differences in amyloid measures are detected in the cerebellum

homeostasis/metabolism
• amyloid beta levels and amyloid plaque burden are increased at 4.5 and 6 months of age, but not at 12 months of age, compared to transgenic mice wild-type for Sorl1 suggesting an acceleration in accumulation of amyloid beta
• some of the largest differences in amyloid measures are detected in the cerebellum

Mouse Models of Human Disease
OMIM IDRef(s)
Alzheimer Disease; AD 104300 J:142501


Mouse Genome Informatics
cx3
    Bace1tm1Pcw/Bace1tm1Pcw
Tg(APP695)3Dbo/0
Tg(PSEN1dE9)S9Dbo/0

involves: 129S1/Sv * 129X1/SvJ * C3H/HeJ * C57BL/6J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
behavior/neurological
N
• mice perform as well as control mice in platform and probe trials in Morris water maze tasks (J:123534)
• in open field test, mice are similar to Bace1tm1Pcw homozygotes, and spend more time in open area at center of field than at periphery
• swim speed is lower than other genotypes and nontransgenic mice in hidden and visible platform trials

nervous system
N
• in 12- or 20-month old mice, no amyloid beta (Abeta) aggregation is detected in brains; no amyloid deposits are found (J:123534)


Mouse Genome Informatics
cx4
    Bace1tm1Pcw/Bace1+
Tg(APP695)3Dbo/0
Tg(PSEN1dE9)S9Dbo/0

involves: 129S1/Sv * 129X1/SvJ * C3H/HeJ * C57BL/6J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
behavior/neurological
• mice are significantly impaired in Morris water maze tasks

nervous system
• high level of amyloid beta aggregates are found in brain at 12 months of age

homeostasis/metabolism
• in 12-month old brains, there is a 27% reduction in amyloid beta aggregates compared to transgenic mice that are wild-type for Bace1; there are no significant differences at 20 months
• in 12-month old brains, there is 37% reduction in percentage of brain volume occupied by amyloid beta deposits, but no difference at 20 months
• high level of amyloid beta aggregates are found in brain at 12 months of age


Mouse Genome Informatics
cx5
    Tg(APP695)3Dbo/0
Tg(PSEN1dE9)S9Dbo/0

involves: 129S1/Sv * 129X1/SvJ * C3H/HeJ * C57BL/6J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
behavior/neurological
• mice travel shorter distance in open-field and show less activity or excursions into central area; mice remain near periphery of apparatus rather than entering open center of field
• 16-18 month-old mice swim farther to find platform and spend less time in platform vicinity than controls

nervous system
• one month following neuron injection with virus expressing short hairpin RNA to silence Bace1, there is a 38% reduction in amyloid beta burden in hippocampus compared to uninjected hippocampus

homeostasis/metabolism
• mice display amyloid beta aggregates at 12 and 20 months
• one month following neuron injection with virus expressing short hairpin RNA to silence Bace1, there is a 38% reduction in amyloid beta burden in hippocampus compared to uninjected hippocampus

Mouse Models of Human Disease
OMIM IDRef(s)
Alzheimer Disease 3 607822 J:123534
Alzheimer Disease; AD 104300 J:123534


Mouse Genome Informatics
cx6
    Tg(APP695)3Dbo/0
Tg(PSEN1dE9)S9Dbo/0

involves: C3H/HeJ * C57BL/6J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• develops diffuse, compact, birefringent congophilic plaques in cortex and hippocampus (J:87691)
• ratio of amyloid beta peptide 40:42 is 0.75:1 (J:87691)
• 150% increase in amyloid beta peptide 42 (J:87691)
• at 7 months of age, mice exhibit amyloid plaques in the hippocampus and cortex (J:104236)

homeostasis/metabolism
• develops diffuse, compact, birefringent congophilic plaques in cortex and hippocampus (J:87691)
• ratio of amyloid beta peptide 40:42 is 0.75:1 (J:87691)
• 150% increase in amyloid beta peptide 42 (J:87691)
• at 7 months of age, mice exhibit amyloid plaques in the hippocampus and cortex (J:104236)


Mouse Genome Informatics
cx7
    Tg(APP695)3Dbo/0
Tg(PSEN1dE9)S9Dbo/0

Not Specified
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• increase in microglial cell activity in retina is observed in 12-15 month old transgenics
• microglia processes in the retina are thicker and display a dendritic-like appearance as compared to control
• microglia density, but not cell body size, is increased in transgenics
• thioflavine-S positive plaques are observed in the retina beginning at 12 months of age
• plaques have radial branches with a central core
• plaque size ranges from 5-20 um, larger plaques are observed at 15-16 months
• plaques appear earlier in females than in males and increase in number over time
• 100% of females and 75% of males have plaques in retina by 15-16 months
• distribution of amacrine cell processes is disrupted as determined by syntaxin 1 staining

vision/eye
• thioflavine-S positive plaques are observed in the retina beginning at 12 months of age
• most plaques (34.7% and 41% respectively) are found in the inner and outer plexiform layers
• thickness of the retinal nuclear layers is similar to control, suggesting that there is no obvious neuronal cell loss
• distribution of amacrine cell processes is disrupted as determined by syntaxin 1 staining
• thioflavine-S positive plaques are first observed in females in the IPL at 12 months
• plaques are first observed in males at 13 months
• plaques are embedded within IPL cholinergic bands
• thioflavine-S positive plaques are first observed in females in the OPL at 12 months
• plaques are first observed in males at 13 months
• amplitudes of a and b waves are decreased in 12-16 month old mice when tested at lower light intensity, but not a higher intensity
• latency and implicit time as determined by ERG measurement are similar to control

immune system
• increase in microglial cell activity in retina is observed in 12-15 month old transgenics
• microglia processes in the retina are thicker and display a dendritic-like appearance as compared to control
• microglia density, but not cell body size, is increased in transgenics

hematopoietic system
• increase in microglial cell activity in retina is observed in 12-15 month old transgenics
• microglia processes in the retina are thicker and display a dendritic-like appearance as compared to control
• microglia density, but not cell body size, is increased in transgenics

homeostasis/metabolism
• thioflavine-S positive plaques are observed in the retina beginning at 12 months of age
• plaques have radial branches with a central core
• plaque size ranges from 5-20 um, larger plaques are observed at 15-16 months
• plaques appear earlier in females than in males and increase in number over time
• 100% of females and 75% of males have plaques in retina by 15-16 months


Mouse Genome Informatics
tg8
    Tg(PSEN1dE9)S9Dbo/0
involves: C3H/HeJ * C57BL/6J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• immunoblotting of of cortical and hippocampal extracts from transgenic mice under conditions that distinguish mouse and human full-length PSEN1 and its endoproteolytic derivatives demonstrates failure of the transgenic protein to undergo endoproteolysis and, instead, accumulation of the full-length mutant human protein in the brain
• endoproteolytic cleavage products of endogenous mouse PSEN1 are 70-90% less abundant in brains of transgenic than of wild-type mice; however, failure of its cleavage does not result in accumulation of the full-length mouse protein


Mouse Models of Human Disease
OMIM IDRef(s)
Alzheimer Disease 3 607822 J:104147
Alzheimer Disease; AD 104300 J:104147