Phenotypes associated with this allele

• Allele Symbol: Tg(PDGFB-PSEN1M146L)2Jhd
• Allele Name: transgene insertion 2, John Hardy
• Allele ID: MGI:2447326
• Summary: 4 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cx1	App^tm1Ck/App^tm1Ck Tg(PDGFB-PSEN1M146L)2Jhd/0	involves: 129 * Black Swiss * C57BL/6 * DBA/2 * SW	MGI:3625136
cx2	Tg(APPSWE)2576Kha/0 Tg(PDGFB-PSEN1M146L)2Jhd/0	involves: C57BL/6 * DBA/2 * SJL	MGI:3717259
cx3	Tg(APPSWE)2576Kha/? Tg(PDGFB-PSEN1M146L)2Jhd/?	involves: C57BL/6 * DBA/2 * SJL * SW	MGI:3711709
cx4	Tg(APPSWE)2576Kha/0 Tg(PDGFB-PSEN1M146L)2Jhd/0	involves: C57BL/6 * DBA/2 * SJL * SW	MGI:5140748

Genotype
MGI:3625136

cx1

• Allelic Composition: App^tm1Ck/App^tm1Ck; Tg(PDGFB-PSEN1M146L)2Jhd/0
• Genetic Background: involves: 129 * Black Swiss * C57BL/6 * DBA/2 * SW

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

nervous system

abnormal microglial cell morphology ( J:102542 )

• microglia are seen associated with compact plaques

amyloid beta deposits ( J:102542 , J:102879 )

• 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^tm1Ck transgenic or App^tm1Ck Tg(PDGFB-PSEN1M146L)2Jhd transgenic mutant mice up to 20 months of age (J:102879)

increased astrocyte number ( J:102542 )

• activated astrocytes are seen associated with plaques

abnormal cholinergic neuron morphology ( J:102542 , J:102879 )

• 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

amyloid beta deposits ( J:102542 , J:102879 )

• 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^tm1Ck transgenic or App^tm1Ck Tg(PDGFB-PSEN1M146L)2Jhd transgenic mutant mice up to 20 months of age (J:102879)

hematopoietic system

abnormal microglial cell morphology ( J:102542 )

• microglia are seen associated with compact plaques

immune system

abnormal microglial cell morphology ( J:102542 )

• microglia are seen associated with compact plaques

Genotype
MGI:3717259

cx2

• Allelic Composition: Tg(APPSWE)2576Kha/0; Tg(PDGFB-PSEN1M146L)2Jhd/0
• Genetic Background: involves: C57BL/6 * DBA/2 * SJL

nervous system

amyloid beta deposits ( J:68670 )

• 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

abnormal astrocyte morphology ( J:68670 )

• 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

gliosis ( J:68670 )

• activated microglia accumulate around amyloid beta deposits from ~ 3 months; number of glia increases with age and amyloid accumulation

astrocytosis ( J:68670 )

• activated astrocytes accumulate around amyloid deposits in frontal cortex of 3 month old mice

homeostasis/metabolism

amyloidosis ( J:68670 )

amyloid beta deposits ( J:68670 )

• 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

Genotype
MGI:3711709

cx3

• Allelic Composition: Tg(APPSWE)2576Kha/?; Tg(PDGFB-PSEN1M146L)2Jhd/?
• Genetic Background: involves: C57BL/6 * DBA/2 * SJL * SW

nervous system

amyloid beta deposits ( J:80429 )

• 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

gliosis ( J:80429 )

• microgliosis and astrocytosis reduced in the hippocampus, and entorhinal cortex

• astrocytosis also reduced in the cingulated cortex

homeostasis/metabolism

amyloid beta deposits ( J:80429 )

• 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

Genotype
MGI:5140748

cx4

• Allelic Composition: Tg(APPSWE)2576Kha/0; Tg(PDGFB-PSEN1M146L)2Jhd/0
• Genetic Background: involves: C57BL/6 * DBA/2 * SJL * SW

renal/urinary system

abnormal renal glomerulus morphology ( J:174270 )

• 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

amyloidosis ( J:174270 )

• 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		DO ID	OMIM ID(s)	Ref(s)
Alzheimer's disease		DOID:10652		J:174270