Mouse Genome Informatics
cx1
    Tg(Gfap-TGFB1)64Lms/0
Tg(PDGFB-APPSwInd)20Lms/0

involves: BALB/c * C57BL/6 * DBA/2 * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
behavior/neurological
• 6-8 month old mutants show increased latencies to locate the hidden platform in the Morris water maze indicating a learning deficit
• 12- and 18-month old mutants show impaired probe trial performance, indicating a memory impairment

cardiovascular system
• mutants exhibit significant collagen accumulation in penetrating intraparenchymal microvessels
• mutants exhibit significant collagen accumulation in penetrating intraparenchymal microvessels and in the surface pial membrane, resulting in increased thickness
• middle cerebral arteries show a 50% loss of ability to dilate in response to acetylcholine and calcitonin gene-related peptide compared to wild-type vessels
• arterial dysfunction is not due to oxidative stress
• by 18 months of age, mutants exhibit impaired maximal diameter decrease during NOS inhibition with N-nitro-L-arginine
• however, contractile response of arteries to endothelin-1 is normal

muscle
• middle cerebral arteries show a 50% loss of ability to dilate in response to acetylcholine and calcitonin gene-related peptide compared to wild-type vessels
• arterial dysfunction is not due to oxidative stress
• by 18 months of age, mutants exhibit impaired maximal diameter decrease during NOS inhibition with N-nitro-L-arginine
• however, contractile response of arteries to endothelin-1 is normal

nervous system
• mutants exhibit significant collagen accumulation in penetrating intraparenchymal microvessels and in the surface pial membrane, resulting in increased thickness
• 18 month old mutants exhibit widespread cerebral amyloid angiopathy in pial, intracortical, and hippocampal brain vessels
• mutants exhibit activated GFAP-positive astrocytes in the cortex; activated astrocytes are distributed in clusters as well as diffusely throughout the cortex
• mutants exhibit significant collagen accumulation in the surface pial membrane, resulting in increased thickness
• about 22-23% reduction in the number of cortical cholinergic fibers in adults and aged-mutants
• mutants exhibit age-dependent amyloid beta plaque deposition in the cortex and hippocampus; 18 month old mutants exhibit parenchymal amyloid beta senile plaques
• mutants exhibit increased levels of soluble and insoluble amyloid beta(1-40) and amyloid beta(1-42) between 6-8 and 12 months of age and further increases in amyloid beta(1-40) at 18 months of age, in the cortex
• glucose uptake is impaired in activated somatosensory cortex of aged mutants after whisker stimulation
• gradual loss of the neuronally-driven hemodynamic response to sensory whisker stimulation

other phenotype
• 18 month old mutants exhibit widespread cerebral amyloid angiopathy in pial, intracortical, and hippocampal brain vessels
• mutants exhibit age-dependent amyloid beta plaque deposition in the cortex and hippocampus; 18 month old mutants exhibit parenchymal amyloid beta senile plaques
• mutants exhibit increased levels of soluble and insoluble amyloid beta(1-40) and amyloid beta(1-42) between 6-8 and 12 months of age and further increases in amyloid beta(1-40) at 18 months of age, in the cortex

Mouse Models of Human Disease
OMIM IDRef(s)
Alzheimer Disease; AD 104300 J:167619


Mouse Genome Informatics
cx2
    Tg(Gfap-TGFB1)64Lms/0
Tg(PDGFB-APPInd)H6Lms/0

involves: BALB/c * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• double transgenic mice display cerebrovascular deposits by 2-3 months of age, while single transgenic littermates have no such deposits at that age

other phenotype
• double transgenic mice display cerebrovascular and meningeal amyloid deposits by 2-3 months of age, while single transgenic littermates have no such deposits at that age
• double transgenic mice display cerebrovascular deposits by 2-3 months of age, while single transgenic littermates have no such deposits at that age


Mouse Genome Informatics
tg3
    Tg(Gfap-TGFB1)64Lms/Tg(Gfap-TGFB1)64Lms
involves: BALB/c * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
growth/size
• at 23 days of age, animals are dwarfs with reduced body weights (6.7 grams) compared to heterozygous or non-transgenic littermates (11.1 grams)

behavior/neurological
• hydroencephaly is accompanied by development of tremors
• hydroencephaly is accompanied by lack of coordination
• hydroencephaly is accompanied by hunched posture
• hydroencephaly is accompanied by development of seizures

nervous system
• hydroencephaly is accompanied by development of seizures
• between 7 and 20 days after birth, all mice develop hydroencephaly
• lateral, third, and fourth ventricles are grossly enlarged; ependymal canal is severely enlarged
• foramina through which cerebrospinal fluid circulates remain open
• sylvian canal is enlarged
• brain regions adjacent to dilated cerebrospinal fluid spaces exhibit atrophy by compression
• mice show characteristic pattern of perivascular astrocytosis
• meningeal coverings are thicker than in hemizygotes or controls

immune system
N
• no inflammatory cell infiltrates are seen in control mice or in transgenic mice displaying hydroencephaly (J:27781)


Mouse Genome Informatics
tg4
    Tg(Gfap-TGFB1)64Lms/0
involves: BALB/c * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• hydroencephaly was observed in only 1% (1/101) of hemizygous mice
• in 12-18 month old mice, prominent amyloid deposits are observed in cerebral blood vessels, whereas none are seen in controls
• mice show characteristic pattern of perivascular astrocytosis, that is less intense than in homozygotes
• meningeal coverings are thicker than controls
• astrocytes secrete increased amounts of bioactive TGF-B1

immune system
N
• no inflammatory cell infiltrates are seen in hemizygous or control mice (J:27781)

other phenotype
• in 12-18 month old mice, prominent amyloid deposits are observed in meninges, whereas none are seen in controls
• in 12-18 month old mice, prominent amyloid deposits are observed in cerebral blood vessels, whereas none are seen in controls