Mouse Genome Informatics
cx1
    Psen1tm1Lpr/Psen1tm1Lpr
Tg(Thy1-APPSL)28Lpr/0

either: 129/Sv or (involves: 129/Sv * C57BL/6)
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• marked reduction in thickness of the hippocampal pyramidal cell layer by 10 months of age
• no amyloid plaques in the CA1/2 pyramidal cell layer
• accelerated rate of A-beta deposition starting at 2.5 months of age
• by 6 months of age deposition has become widespread and numerous in cortical, hippocampal and thalamic areas
• astrocytic and microglial activation around amyloid plaques

other phenotype
• accelerated rate of A-beta deposition starting at 2.5 months of age
• by 6 months of age deposition has become widespread and numerous in cortical, hippocampal and thalamic areas
• astrocytic and microglial activation around amyloid plaques

Mouse Models of Human Disease
OMIM IDRef(s)
Alzheimer Disease 3 607822 J:93770
Alzheimer Disease; AD 104300 J:93770


Mouse Genome Informatics
cx2
    Psen1tm1Lpr/Psen1tm1Lpr
Tg(Thy1-APPSL)28Lpr/0

involves: 129 * C57BL/6 * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• amyloid beta plaques form but no intracellular aggregates are seen
• numerous plaques form between 2 and 6 months of age and the pathology increases with age
• unlike in the frontal cortex, no neuronal loss is detected in the thalamus
• amyloid plaques are located frequently within the granular cell layer of the dentate gyrus
• the granule cell layer is less densely packed at 12 months of age compared to 2 months of age
• the granule cell border is often frayed
• ectopic cells that are often orientated towards extracellular amyloid deposits can be detected at 2 months of age
• decrease in the number of dentate gyrus granule cells at 12 months of age
• decrease in the number of dentate gyrus granule cells at 12 months of age
• massive intra- and extra-cellular amyloid beta deposits are detected in the frontal cortex at as early as 1.5 months of age, before significant plaque formation is detected
• by 6 months of age intracellular accumulations are no longer a prominent pathological feature
• a 28% and 35% loss of neurons is seen in the frontal cortex at 6 and 12 months of age, respectively, compared to age-matched controls
• frontal cortex volume is reduced compared to controls at 6 and 12 months of age
• thickened and irregularly shaped neurites are seen in the medulla at 14 months of age
• axonal spheroids are detected in pons and cortical areas at 6 months of age and in the spinal cord mostly along the anterior margin of the ventral horn and less frequently in the intermediolateral and dorsal horn
• at 10 and 14 months of age axonal spheroids are detected in pons, cortex, medulla, midbrain, hippocampus, corpus callosum and striatum
• larger axonal varicosities are seen in the medulla at 14 months of age
• large axonal dilatations are localized in white matter fiber tracts in close vicinity to the ventral horn in the spinal cord
• dilated axons often display thinned or focally absent myelin sheaths
• increased deposition of myelin ovoids in the white matter
• a 28% and 35% loss of neurons is seen in the frontal cortex at 6 and 12 months of age, respectively, compared to age-matched controls
• some plaques are detected at 2 months of age in the cervical spinal cord and plaques increase with age (J:128106)
• plaque formation is higher in the cervical spinal cord compared to the thoracic and lumbar regions (J:128106)
• plaques are almost exclusively found in the gray matter (J:128106)
• amyloid plaques are located frequently within the granular cell layer of the dentate gyrus (J:139736)
• significant plaque formation is detected in the frontal cortex by 2 months of age (J:146342)
• from 6 to 12 months of age plaques become more densely packed (J:146342)

homeostasis/metabolism
• significant decrease in plasma cholesterol between 2 and 6 months of age that is not seen in wild-type controls or either single transgenic mice
• basal cholesterol levels are increase compared to wild-type controls probably as a result of differences in strain background

behavior/neurological
• at 10 and 14 months of age
• impaired performance in a balance beam test at 10 and 14 months of age

growth/size
• at 10 and 14 months of age compared to mutant mice not carrying the transgene

other phenotype
• some plaques are detected at 2 months of age in the cervical spinal cord and plaques increase with age (J:128106)
• plaque formation is higher in the cervical spinal cord compared to the thoracic and lumbar regions (J:128106)
• plaques are almost exclusively found in the gray matter (J:128106)
• amyloid plaques are located frequently within the granular cell layer of the dentate gyrus (J:139736)
• significant plaque formation is detected in the frontal cortex by 2 months of age (J:146342)
• from 6 to 12 months of age plaques become more densely packed (J:146342)

Mouse Models of Human Disease
OMIM IDRef(s)
Alzheimer Disease; AD 104300 J:128106


Mouse Genome Informatics
cx3
    Tg(Hmgcr-PSEN1*M146L)#Lpr/0
Tg(Thy1-APPSL)28Lpr/0

involves: C57BL/6 * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• non-corrected intracranial and brain volumes are reduced compared to Tg(Hmgcr-PSEN1*M146L)#Lpr single transgenics at 10 weeks of age
• corrected brain volumes are strongly decreased with age
• in aged mice compared to Tg(Hmgcr-PSEN1*M146L)#Lpr single transgenics
• significant increase in brain length with age compared to Tg(Hmgcr-PSEN1*M146L)#Lpr single transgenics
• surface area of the internal capsule does not increase with age unlike in Tg(Hmgcr-PSEN1*M146L)#Lpr single transgenics
• decrease in thickness of the caudal corpus callosum with age
• decrease in fornix diameter in aged mice
• age-related decline in mean synaptic bouton densities within the stratum lucidum of area CA3
• age-related decline in mean synaptic bouton densities and in mean volume
• age-related decline in mean synaptic bouton densities in area CA1?2
• clusters of swollen and abnormally distorted neuritic profiles are seen
• age-related decline in mean synaptic bouton densities within the hippocampal molecular cell layer, stratum lucidum of area CA3, and stratum radiatum of area CA1?2
• plaques are seen at 6 months of age (J:86694)
• detected in the hippocampus at 4.5 and 17 months of age (J:99507)
• abundant amyloid beta neuropil deposits in hippocampal and cortical areas in aged mice (J:128243)
• global brain atrophy in aged mice

homeostasis/metabolism
• significant decrease in plasma cholesterol between 3 and 13 months of age that is not seen in wild-type controls
• plasma cholesterol levels are reduced compared to wild-type controls at 13 months of age but not at 3 months of age

other phenotype
• plaques are seen at 6 months of age (J:86694)
• detected in the hippocampus at 4.5 and 17 months of age (J:99507)
• abundant amyloid beta neuropil deposits in hippocampal and cortical areas in aged mice (J:128243)

growth/size
• brain weight to body weight ratio is increased compared to Tg(Hmgcr-PSEN1*M146L)#Lpr single transgenics at 24 months of age
• in aged mice compared to Tg(Hmgcr-PSEN1*M146L)#Lpr single transgenics

Mouse Models of Human Disease
OMIM IDRef(s)
Alzheimer Disease; AD 104300 J:86694 , J:99507


Mouse Genome Informatics
tg4
    Tg(Thy1-APPSL)28Lpr/0
B6.Cg-Tg(Thy1-APPSL)28Lpr
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• enhanced lethality at young ages (less than 4 months of age)

behavior/neurological
• spend more time in the closed arms of an elevated plus maze at 15 months of age compared to age matched controls
• cross fewer segments and show a reduced latency to fall in a stationary beam test at 15 months of age
• significant decrease in latency to fall in a wire grid assay at 3 and 15, but not at 6, months of age
• significant decrease in latency to fall in a coat hanger assay at 15 months of age
• at 3, 6, and 15 months of age in an open field test
• activity decreases with age

nervous system
• increase in brain length but not weight

growth/size
• from 3 to 15 months of age

other phenotype


Mouse Genome Informatics
tg5
    Tg(Thy1-APPSL)28Lpr/0
involves: C57BL/6 * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• levels of SDS-soluble amyloid beta protein are higher in females than in males at 3 months of age
• age-related decline in mean synaptic bouton densities
• age-related decline in mean synaptic bouton densities in area CA1?2
• clusters of swollen and abnormally distorted neuritic profiles are seen
• age-related decline in mean synaptic bouton densities within the hippocampal molecular cell layer and stratum radiatum of area CA1?2
• plaques are seen at 6 months of age (J:86694)
• detected in the hippocampus at 17 months of age (J:99507)
• elevated levels of lipid peroxidation products in brain homogenates in females at 3 months of age and in males and females at 12 months of age
• reduced levels of antioxidant enzymes at 3 and 12 months of age
• impaired mitochondrial function

cellular
• mitochondrial membrane potentials and ATP levels are reduced in dissociated brain cells at 3 months of age
• inhibition of complex IV and significantly reduced cytochrome c oxidase activity in cerebral isolated mitochondria
• state 3 and state 4 respiration are significantly reduced in freshly isolated cerebral mitochondria at 17 months of age

other phenotype
• plaques are seen at 6 months of age (J:86694)
• detected in the hippocampus at 17 months of age (J:99507)

Mouse Models of Human Disease
OMIM IDRef(s)
Alzheimer Disease; AD 104300 J:86694 , J:99507