Mouse Genome Informatics
cn1
    Psen1tm1Vln/Psen1tm1Vln
Tg(Thy1-APPLon)2Vln/0
Tg(Thy1-cre)1Vln/0

involves: FVB/N
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
behavior/neurological
• retention of object recognition is normal at 1 hr after training but testing of animals 3 hours after familiarization with an object reveals significant impairment relative to controls

nervous system
N
• no thioflavin-S-reactive amyloid plaques or diffuse amyloid deposits are detected in mice up to 18 months of age (J:87229)
• with tetanic stimulation of hippocampal slices, after an initial slight decrease, the slope of the fEPSP approached control levels; LTP in transgenic brain slices is comparable to controls


Mouse Genome Informatics
cx2
    Tg(Hmgcr-PSEN1*M146L)#Lpr/0
Tg(Thy1-APPLon)2Vln/0

involves: C57BL/6 * CBA * FVB/N
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• plaques are seen at 6 months of age
• as soon as detectable, a large number of deposits have a fibrillar conformation

other phenotype
• plaques are seen at 6 months of age
• as soon as detectable, a large number of deposits have a fibrillar conformation

Mouse Models of Human Disease
OMIM IDRef(s)
Alzheimer Disease; AD 104300 J:86694


Mouse Genome Informatics
cx3
    Tg(Thy1-APPLon)2Vln/0
Tg(Thy1-BACE1)16Vln/0

involves: C57BL/6 * DBA * FVB/N
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• by 15 months, subiculum is almost totally covered with diffuse and senile plaques
• at 15 months and older, surface of cerebral cortex is occupied by thioflavin-S- and amyloid beta-positive deposits is 3-5-fold greater than in age-matched Tg(APPV717I)1130Kha mice
• decrease in vascular amyloid deposition is found in double transgenics relative to single mutant animals
• dystrophic neurites with swollen and distorted neuritic profiles are identified in brains of mice
• fibrillar thioflavin-S positive amyloid plaques are significantly increased in subiculum region of brain compared to Tg(APPV717I)1130Kha single transgenics

other phenotype
• total levels of intact amyloid beta-40 and-42 peptides are increased by ~3-fold in older mice relative to single transgenic mice
• decrease in vascular amyloid deposition is found in double transgenics relative to single mutant animals
• fibrillar thioflavin-S positive amyloid plaques are significantly increased in subiculum region of brain compared to Tg(APPV717I)1130Kha single transgenics

Mouse Models of Human Disease
OMIM IDRef(s)
Alzheimer Disease; AD 104300 J:93635


Mouse Genome Informatics
cx4
    Tg(Thy1-APPLon)2Vln/0
Tg(Thy1-PSEN1*A246E)2Vln/0

involves: FVB/N
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• amyloid deposition occurs at 6-9 months in double mutants compared to 12-15 months in single APP transgenic mice; Abeta 42/Abeta 40 ratio is increased in young and aged mice with ratio of 3.11 at 15 months compared to 0.43 in Tg(Thy1-APP*V642I)2Vln mice at 6-9 months
• plaque-associated peptides are dramatically high in brains of double mutant mice aged 6-9 months

other phenotype
• amyloid deposition occurs at 6-9 months in double mutants compared to 12-15 months in single APP transgenic mice; Abeta 42/Abeta 40 ratio is increased in young and aged mice with ratio of 3.11 at 15 months compared to 0.43 in Tg(Thy1-APP*V642I)2Vln mice at 6-9 months
• plaque-associated peptides are dramatically high in brains of double mutant mice aged 6-9 months


Mouse Genome Informatics
tg5
    Tg(Thy1-APPLon)2Vln/0
(C57BL/6 x FVB/N)F1
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
behavior/neurological
N
• in forced swim test and a visible platform paradigm, transgenic mice perform comparably to controls indicating normal motor abilities and motivation (J:53800)
• in Morris water maze test hidden platform tests, 3-6 month old mice show significantly longer escape latencies (measure of spatial learning and memory) than non-transgenic controls
• when platform is removed, 3-6 month old mutants spend less time crossing area of the platform's former location than controls, indicating impaired cognition


Mouse Genome Informatics
tg6
    Tg(Thy1-APPLon)2Vln/0
involves: C57BL/6 * CBA * FVB/N
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• clusters of swollen and abnormally distorted neuritic profiles are seen
• plaques are seen at 13 months of age

other phenotype
• plaques are seen at 13 months of age

Mouse Models of Human Disease
OMIM IDRef(s)
Alzheimer Disease; AD 104300 J:86694


Mouse Genome Informatics
tg7
    Tg(Thy1-APPLon)2Vln/0
involves: FVB/N
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• 47.1% of animals died by 180 days of age; mortality by 360 days is 70.6% compared to 4.3% in controls

nervous system
• less than 15% of mice older than 6 months display spontaneous seizures
• by 15 months, subiculum is almost totally covered with diffuse and senile plaques
• amyloid deposits are found in the parenchyma and in cortical and leptimenigeal arterioles in brains at 16 months
• dystrophic neurites with swollen and distorted neuritic profiles are identified in brains of mice
• diffuse amyloid plaques and compact neuritic plaques are detected in all mice 13-18 months old, most abundant in the hippocampus and cortex while occasionally seen in the thalamus, fimbria, external capsule, pontine nuclei, and white matter; plaques contain high amounts of the Abeta 42 peptidediffuse amyloid plaques and compact neuritic plaques are detected in all mice 13-18 months old, most abundant in the hippocampus and cortex while occasionally seen in the thalamus, fimbria, external capsule, pontine nuclei, and white matter; plaques contain high amounts of the Abeta 42 peptide (J:53800)
• mice younger than 12 months do not exhibit amyloid deposits (J:53800)
• levels of plaque peptides extracted with guanidinium hydrochloride increase exponentially in mutants >15 months of age; plaque associated peptides are not detected in brains of mice at 6-9 months of age (J:64209)
• subiculum region of brain is loaded amyloid deposits starting at 10 months of age (J:93635)
• tetanic stimulation in hippocampal brain slices triggers significantly impaired LTP; LTP progressively decreases in brain slices (J:87229)

behavior/neurological
• ambulation measured in a corner-crossing variant upon transfer to a new cage is reduced relative to controls at 4-9 weeks of age, 12-17, and 20-52 weeks with differences becoming more pronounced with age
• mice exhibit increased episodes of agitation and spontaneous activity by 8 weeks of age onward
• less than 15% of mice older than 6 months display spontaneous seizures

other phenotype
• in brains of 10-12 month-old mice, diffuse and senile amyloid plaques are present and increase exponentially with age (J:87229)
• amyloid deposits are found in the parenchyma and in cortical and leptimenigeal arterioles in brains at 16 months
• diffuse amyloid plaques and compact neuritic plaques are detected in all mice 13-18 months old, most abundant in the hippocampus and cortex while occasionally seen in the thalamus, fimbria, external capsule, pontine nuclei, and white matter; plaques contain high amounts of the Abeta 42 peptidediffuse amyloid plaques and compact neuritic plaques are detected in all mice 13-18 months old, most abundant in the hippocampus and cortex while occasionally seen in the thalamus, fimbria, external capsule, pontine nuclei, and white matter; plaques contain high amounts of the Abeta 42 peptide (J:53800)
• mice younger than 12 months do not exhibit amyloid deposits (J:53800)
• levels of plaque peptides extracted with guanidinium hydrochloride increase exponentially in mutants >15 months of age; plaque associated peptides are not detected in brains of mice at 6-9 months of age (J:64209)
• subiculum region of brain is loaded amyloid deposits starting at 10 months of age (J:93635)

Mouse Models of Human Disease
OMIM IDRef(s)
Alzheimer Disease; AD 104300 J:93635