Mouse Genome Informatics
cx1
    Tg(Prnp-ITM2B*)6Jckr/0
Tg(Thy1-APP)3Somm/0

B6.Cg-Tg(Prnp-ITM2B*)6Jckr Tg(Thy1-APP)3Somm
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
other phenotype
• mice exhibit an accumulation of Dan-amyloid in separate plaques from amyloid beta plaques
• at 13 months, mice exhibit a 70% reduction in neocortical amyloid beta deposition compared with Tg(Thy1-APP)3Somm mice

nervous system
• at 13 months, mice exhibit a 70% reduction in neocortical amyloid beta deposition compared with Tg(Thy1-APP)3Somm mice


Mouse Genome Informatics
cx2
    Tnfrsf1atm1Imx/Tnfrsf1atm1Imx
Tg(Thy1-APP)3Somm/0

involves: C57BL/6 * C57BL/6J * DBA/2
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
N
• at 24 months, mice exhibit little neuronal loss unlike Tg(Thy1-APP)3Somm mice (J:134832)
• mice exhibit less microglial activation compared with Tg(Thy1-APP)3Somm mice
• mice exhibit reduced cerebral amyloid angiopathy compared with Tg(Thy1-APP)3Somm mice
• at 24 months, mice exhibit reduced amyloid plaques compared with Tg(Thy1-APP)3Somm mice

other phenotype
• mice exhibit reduced cerebral amyloid angiopathy compared with Tg(Thy1-APP)3Somm mice
• at 24 months, mice exhibit reduced amyloid plaques compared with Tg(Thy1-APP)3Somm mice

behavior/neurological
N
• mice exhibit normal exploratory learning and memory retention unlike Tg(Thy1-APP)3Somm mice (J:134832)

hematopoietic system
• mice exhibit less microglial activation compared with Tg(Thy1-APP)3Somm mice

immune system
• mice exhibit less microglial activation compared with Tg(Thy1-APP)3Somm mice


Mouse Genome Informatics
cx3
    Abca1tm1Jdm/Abca1tm1Jdm
Tg(Thy1-APP)3Somm/0

involves: C57BL/6J * DBA/1LacJ * DBA/2
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• fewer than expected mice are present at weaning

nervous system
• mice exhibit more cerebral amyloid angiopathy-associated cerebral hemorrhage than Tg(Thy1-APP)3Somm mice
• at 13 months, mice exhibit more cerebral amyloid angiopathy than in Tg(Thy1-APP)3Somm mice

other phenotype
• mice exhibit a 2-fold increase in insoluble beta-amyloid in the brain compared with Tg(Thy1-APP)3Somm mice
• at 13 months, mice exhibit more cerebral amyloid angiopathy than in Tg(Thy1-APP)3Somm mice

cardiovascular system
• mice exhibit more cerebral amyloid angiopathy-associated cerebral hemorrhage than Tg(Thy1-APP)3Somm mice


Mouse Genome Informatics
tg4
    Tg(Thy1-APP)3Somm/0
B6.Cg-Tg(Thy1-APP)3Somm
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• vascular amyloid is associated with ectopic entorhinal boutons
• axons that line the periphery of beta-amyloid plaques exhibit swelling unlike in wild-type mice
• entorhinal fibers extend outside the termination zone unlike in wild-type mice
• commissure axons extend into the outer molecular layer unlike in wild-type mice
• amyloid plaques are associated with alterations in axonal growth and ectopic synaptic differentiation
• vascular amyloid is associated with ectopic entorhinal boutons
• amyloid plaques are associated with alterations in axonal growth and ectopic synaptic differentiation

behavior/neurological
• at 3 months, mice exhibit lower light ambulation compared with wild-type mice
• at 6 months, mice exhibit increased in the ratio of dark to light ambulation during the second half of the active phase compared with wild-type mice
• at 12 months, circadian locomotor patterns are more constant than in wild-type mice
• at 12 months, mice exhibit increased dark and total ambulation compared with wild-type mice
• at 12 months, dark ambulation level is bimodal unlike in wild-type mice
• in an isolation-induced/resident-intruder paradigm, mice exhibit a 4.6- and 59-fold increase in aggression at 6 and 12 months, respectively, compared with wild-type mice
• at 6 months during the first 2 hours
• impaired acquisition in the Morris water maze; the number of quadrant entries and the escape latencies are higher than in controls
• however, mutants are unaffected in open-field, elevated plus-maze, emergence tests, tests measuring motor coordination, during the probe trial and while swimming towards a visible platform
• 67% of animals exhibit myoclonic jumping behavior in home cage
• reduced number of horizontal and vertical movements in the photocell monitor
• overnight at 12 months

other phenotype
• vascular amyloid is associated with ectopic entorhinal boutons
• amyloid plaques are associated with alterations in axonal growth and ectopic synaptic differentiation

growth/size
• 29% weight reduction compared to wild-type

Mouse Models of Human Disease
OMIM IDRef(s)
Alzheimer Disease; AD 104300 J:80449


Mouse Genome Informatics
tg5
    Tg(Thy1-APP)3Somm/0
involves: C57BL/6J * DBA/2
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• mice exhibit aneurysm-like vasodilation unlike in wild-type mice
• mice exhibit blood vessel ruptures that range from microhemorrhages to large hematomas unlike wild-type mice
• mice exhibit leakage in the blood-brain barrier unlike wild-type mice
• mutants exhibit inflammatory responses in the brain, showing a massive glial response
• loss of pyramidal neurons in the vicinity of amyloid beta deposits in the CA3 area
• in the neocortex, hippocampus, and thalamus and to a lesser degree in other regions such as septum, striatum, brainstem, and white matter (J:67583)
• local distortion of the cholinergic fiber network is seen in the vicinity of plaques
• local loss of neurons in the vicinity of plaques
• at 24 months
• develop amyloid beta deposits in the neocortex and hippocampus starting at 6 months of age, which increase in size and number with age (J:44603)
• by 24 months of age, deposits occupy a substantial area of the neocortex and hippocampus and are found in the thalamus and olfactory nucleus and are isolated in the caudate putamen (J:44603)
• develop almost exclusively congophilic plaques already at their first appearance (J:44603)
• at 24 months (J:134832)

other phenotype
• in the neocortex, hippocampus, and thalamus and to a lesser degree in other regions such as septum, striatum, brainstem, and white matter (J:67583)
• develop amyloid beta deposits in the neocortex and hippocampus starting at 6 months of age, which increase in size and number with age (J:44603)
• by 24 months of age, deposits occupy a substantial area of the neocortex and hippocampus and are found in the thalamus and olfactory nucleus and are isolated in the caudate putamen (J:44603)
• develop almost exclusively congophilic plaques already at their first appearance (J:44603)
• at 24 months (J:134832)

immune system
• mice exhibit cerebral amyloid angiopathy associated vasculitis unlike wild-type mice
• mutants exhibit inflammatory responses in the brain, showing a massive glial response

cardiovascular system
• mice exhibit aneurysm-like vasodilation unlike in wild-type mice
• mice exhibit smooth muscle cell degeneration in amyloid laden blood vessels unlike wild-type mice
• bicuculline-treated mice exhibit delayed and reduced amplitude of changes in cerebral blood volume compared with similarly treated wild-type mice
• at 25 months, acetazolamide-treated mice exhibit a smaller increase in the percent change of cerebral blood volume compared with similarly treated wild-type mice
• mice exhibit blood vessel ruptures that range from microhemorrhages to large hematomas unlike wild-type mice
• mice exhibit leakage in the blood-brain barrier unlike wild-type mice
• mice exhibit cerebral amyloid angiopathy associated vasculitis unlike wild-type mice

muscle
• mice exhibit smooth muscle cell degeneration in amyloid laden blood vessels unlike wild-type mice

homeostasis/metabolism
• bicuculline-treated mice exhibit delayed and reduced amplitude of changes in cerebral blood volume compared with similarly treated wild-type mice
• at 25 months, acetazolamide-treated mice exhibit a smaller increase in the percent change of cerebral blood volume compared with similarly treated wild-type mice
• during posthypoxic recovery, the spike amplitude in hippocampal region CA1 after stimulation of Schaffer collaterals in region CA3 is less than in similarly treated wild-type mice
• at 4 months, hypoxic tolerance is impaired compared to in similarly treated wild-type mice

behavior/neurological
• at 6 months, mice exhibit reduced exploratory learning compared with wild-type mice
• object recognition is impaired compared to in wild-type mice

hematopoietic system