Mouse Genome Informatics
hm1
    Apptm1Ck/Apptm1Ck
involves: 129
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
behavior/neurological
• in the elevated plus maze, mice show decreased open time and increased closed time

nervous system
• corticotropin releasing factor levels are increased in the lateral dorsal bed nucleus of the stria terminalis


Mouse Genome Informatics
cx2
    Apptm1Ck/Apptm1Ck
Psen1tm1Mpm/Psen1tm1Mpm
Tg(MAPT)8cPdav/0

B6.Cg-Psen1tm1Mpm Apptm1Ck Tg(MAPT)8cPdav
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
behavior/neurological
• in the elevated plus maze, 4 month old mice spend less time on the open arm, indicating increased anxiety
• however, mice show normal nociception in the hot plate assay
• mice show slightly higher pre-shock freezing frequency and increased contextual freezing frequency at 4 and 12 months of age, indicating exaggerated fear response
• mice show increased contextual freezing frequency at 4 and 12 months of age
• however, cued freezing frequency is unaffected and mice do not exhibit spatial memory deficits in the Morris water maze
• in the open field, the total travel distance is reduced at 12, but not 4, months of age, indicating age-dependent reduced activity

homeostasis/metabolism
• mice exhibit amyloid beta plaques on the outer edge of the cortex at 18-22 months of age which progress into inner layers of the cortex and hippocampus by 26-29 months of age

nervous system
• mice exhibit amyloid beta plaques on the outer edge of the cortex at 18-22 months of age which progress into inner layers of the cortex and hippocampus by 26-29 months of age
• increase in phosphorylated tau in the cortex and hippocampus

Mouse Models of Human Disease
OMIM IDRef(s)
Alzheimer Disease; AD 104300 J:209782


Mouse Genome Informatics
cx3
    Apptm1Ck/Apptm1Ck
Psen1tm1Mpm/Psen1tm1Mpm

involves: 129 * 129S1/Sv * 129X1/SvJ
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• mice exhibit decreased amyloid load compared with Apptm3.1Zhe Psen1tm1Mpm double homozygotes
• corticotropin releasing factor levels are increased in the lateral dorsal bed nucleus of the stria terminalis and the paraventricular nucleus

homeostasis/metabolism
• mice exhibit an increase in resting levels of circulating corticosterone
• mice exhibit decreased amyloid load compared with Apptm3.1Zhe Psen1tm1Mpm double homozygotes

behavior/neurological
• in the elevated plus maze, mice spend more time in the closed arms and less time in the open arms and make fewer entries into the open arms and navigate less distance on the open arms, indicating increased levels of anxiety
• in the light-dark box test, mice spend more time in the closed portion of the box and less time in the open side, make fewer entries to the light side of the box, and spend on average more time on each visit to the dark side, suggesting an increase in hiding behavior and reduction in exploring
• mice show increased freezing in the context in which they received the shock compared to wild-type mice but show similar levels of freezing as wild-type mice in cued fear (in response to sound)
• during the cued trial, mice show increased baseline freezing levels in the 3 minutes before presentation of sound, however increased baseline freezing is not seen before mice are shocked
• mice show increased freezing in the context in which they received the shock compared to wild-type mice but show similar levels of freezing as wild-type mice in cued fear (in response to sound), indicating increased contextual fear
• however, hot plate assay shows normal nociception
• in the alternation T-maze test, mice show decreased alternation, indicating reduced working memory

Mouse Models of Human Disease
OMIM IDRef(s)
Alzheimer Disease; AD 104300 J:191170


Mouse Genome Informatics
cx4
    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
cx5
    Apptm1Ck/Apptm1Ck
Tg(PDGFB-PSEN1)1Jhd/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
• areas of higher density of cholinergic fibers in the cortex at 20 months of age
• however, mice do not form amyloid beta plaques