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
• microglia are seen associated with compact plaques
• mice develop two types of amyloid plaques beginning at 9 months of age, either compact, typically round (compact) plaque which are seen at early stages or fluffy amyloid beta material (diffuse) plaque which are seen at later stages (J:102542)
• at 12 months of age, plaques are seen in the frontal, parietal, occipital, cingulate, and temporal cortices, in the hippocampus, and in the white matter, most often in the corpus callosum (J:102542)
• at 18 months, amyloid beta deposits develop in the entorhinal and piriform cortices such that 21 months, density is high in the piriform cortex but relatively low in the entorhinal cortex (J:102542)
• at 18 months, plaques spread to extracortical sites, mainly to the striatum and septum and at 21 months, they are seen in the colliculi (thalamus, amygdala, olfactory bulb, and olfactory nucleus but not in the cerebellum, pons, or medulla oblongata (J:102542)
• mice develop vascular amylod-beta deposits in leptomeningeal vessels and their larger intracortical branches at 12 months of age (J:102542)
• however, mice do not develop neurofibrillary tangles or show signs of neurodegeneration (J:102542)
• 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 (J:102879)
• activated astrocytes are seen associated with plaques
• mice develop abnormal cholinergic fiber aggregates and enlarged terminals after 12 months of age (J:102542)
• 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 (J:102879)
• 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 (J:102879)
• 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 (J:102879)

homeostasis/metabolism
• mice develop two types of amyloid plaques beginning at 9 months of age, either compact, typically round (compact) plaque which are seen at early stages or fluffy amyloid beta material (diffuse) plaque which are seen at later stages (J:102542)
• at 12 months of age, plaques are seen in the frontal, parietal, occipital, cingulate, and temporal cortices, in the hippocampus, and in the white matter, most often in the corpus callosum (J:102542)
• at 18 months, amyloid beta deposits develop in the entorhinal and piriform cortices such that 21 months, density is high in the piriform cortex but relatively low in the entorhinal cortex (J:102542)
• at 18 months, plaques spread to extracortical sites, mainly to the striatum and septum and at 21 months, they are seen in the colliculi (thalamus, amygdala, olfactory bulb, and olfactory nucleus but not in the cerebellum, pons, or medulla oblongata (J:102542)
• mice develop vascular amylod-beta deposits in leptomeningeal vessels and their larger intracortical branches at 12 months of age (J:102542)
• however, mice do not develop neurofibrillary tangles or show signs of neurodegeneration (J:102542)
• 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 (J:102879)

hematopoietic system
• microglia are seen associated with compact plaques

immune system
• microglia are seen associated with compact plaques


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