Mouse Genome Informatics
cx1
    Apptm1Ck/Apptm1Ck
Tg(PDGFB-PSEN1M146L)2Jhd/0

involves: 129 * Black Swiss * C57BL/6 * DBA/2 * SW
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• amyloid plaques are detected in the brains of these mutant transgenic mice but not in App transgenic or App Tg(PDGFB-PSEN1M146L)2Jhd transgenic mutant mice up to 20 months of age
• in 1-year old animals, a relatively high number of cholinergic fiber aggregates in the cortex are observed in transgenic; at 20 months of age, a few such areas of densed cholinergic fiber aggregations are observed in other APP-targeted mice
• cholinergic fibers of large diameter are seen in layer 1 of the entorhinal cortex in mutant transgenic mice more prominently than in the other strains, but such fibers are present even in controls
• clusters of ballooned and spherical acetylcholine-immunoreactive terminals are observed in the periphery of compact amyloid plaques around the amyloid core in 12-month old animals, and numbers increase with age and plaque load

homeostasis/metabolism
• amyloid plaques are detected in the brains of these mutant transgenic mice but not in App transgenic or App Tg(PDGFB-PSEN1M146L)2Jhd transgenic mutant mice up to 20 months of age


Mouse Genome Informatics
cx2
    Tg(APPSWE)2576Kha/0
Tg(PDGFB-PSEN1M146L)2Jhd/0

involves: C57BL/6 * DBA/2 * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• at <3 months of age, mice show amyloid beta deposits in frontal cortex; with age, deposits spread throughout cortex, and to the hippocampus, thalamus and dentate gyrus
• by 1 year of age, deposits are widely observed, with no apparent increase in total amount of amyloid deposited after this age
• some fibrillar amyloid beta deposits are detected in the frontal cortex of youngest mice, with absence of deposits in more caudal regions; number of fibrillar deposits increases up to 1 year of age, with area covered by fibrillar deposits increasing up to 2 years of age
• at 1 year, area covered by fibrillar deposits is ~50% of total amyloid beta, but comprises majority of total covered area by 2.5 years of age
• ins some areas of cortex in older animals,astrocytes appear dystrophic and are no longer closely associated with plaques, although nearby plaques are associated with activated glial cells
• activated microglia accumulate around amyloid beta deposits from ~ 3 months; number of glia increases with age and amyloid accumulation
• activated astrocytes accumulate around amyloid deposits in frontal cortex of 3 month old mice

homeostasis/metabolism
• at <3 months of age, mice show amyloid beta deposits in frontal cortex; with age, deposits spread throughout cortex, and to the hippocampus, thalamus and dentate gyrus
• by 1 year of age, deposits are widely observed, with no apparent increase in total amount of amyloid deposited after this age
• some fibrillar amyloid beta deposits are detected in the frontal cortex of youngest mice, with absence of deposits in more caudal regions; number of fibrillar deposits increases up to 1 year of age, with area covered by fibrillar deposits increasing up to 2 years of age
• at 1 year, area covered by fibrillar deposits is ~50% of total amyloid beta, but comprises majority of total covered area by 2.5 years of age


Mouse Genome Informatics
cx3
    Tg(APPSWE)2576Kha/?
Tg(PDGFB-PSEN1M146L)2Jhd/?

involves: C57BL/6 * DBA/2 * SJL * SW
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• treatment with antibody to CD40L results in more diffuse beta-amyloid plaques
• equal levels of alpha- and beta-CTF
• antibody to CD40L produces increased levels of circulating beta amyloid
• microgliosis and astrocytosis reduced in the hippocampus, and entorhinal cortex
• astrocytosis also reduced in the cingulated cortex

homeostasis/metabolism
• treatment with antibody to CD40L results in more diffuse beta-amyloid plaques
• equal levels of alpha- and beta-CTF
• antibody to CD40L produces increased levels of circulating beta amyloid


Mouse Genome Informatics
cx4
    Tg(APPSWE)2576Kha/0
Tg(PDGFB-PSEN1M146L)2Jhd/0

involves: C57BL/6 * DBA/2 * SJL * SW
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
renal/urinary system
• kidney glomeruli are dilated probably due to obstruction from the amyloid in the lumen or walls of medullary tubules especially in the papilla

homeostasis/metabolism
• some mutants older than 18 months exhibit amyloid deposits in the spleen and kidneys, and occasionally in the liver, ovary and/or heart
• amyloid is deposited concentrically in the perifollicular sheath, partly or completely encircling the follicles in the spleen
• in the liver, amyloid deposit is in the walls of sinusoids or central veins
• in the kidney, amyloid deposits are seen in the glomeruli
• amyloid deposits in the heart are not composed of amyloid-beta peptide, but rather amyloid A

Mouse Models of Human Disease
OMIM IDRef(s)
Alzheimer Disease; AD 104300 J:174270