Mouse Genome Informatics
tg
    Tg(Thy1-APPSwDutIowa)BWevn/0
involves: C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
       
nervous system
• activation of microglial and astrocytes is elevated in cortex
• microglial cells show significantly increased levels of complement proteins C1q, C3 and C4
• levels of amyloid beta-40 and -42 peptides are 12- and 14-fold higher in forebrain microvessels than in whole forebrain homogenates at 12 months of age; at ~3 months, levels in vasculature of forebrains is higher than whole forebrain tissue (J:89848)
• vascular amyloid beta accumulation is prominent in the thalamus and subiculum, and increases with age such that 45-55% of vessels are affected at 12 months of age; at ~6 months of age, amyloid beta deposits in and around microvessels in the thalamus and subiculum are observed (J:89848)
• microvascular amyloid beta accumulations are mainly fibrillar (J:89848)
• some arterioles in these brain regions show strong vascular and perivascular amyloid beta depostion, while blood vessel-rich regions like the hippocampal fissure show large accumulations of perivascular amyloid beta (J:89848)
• evidence of microhemorrhage is observed in microvessels with amyloid beta deposits (J:89848)
• microvascular fibrillar amyloid beta accumulation is observed in thalamic and hippocampal regions (J:124911)
• astrocyte numbers and density are enhanced in thalamic and cortical regions where fibrillar amyloid beta deposits are prominent
• over the course of 1 year, progressive and robust accumulation of insoluble amyloid beta-40 and -42 peptides is observed in mouse brains; increase in peptides is first observed at 3 months and increases markedly by 12 months (J:89848)
• soluble and insoluble amyloid beta-40 peptide levels are 10-fold higher than amyloid beta-42 peptide levels (J:89848)
• amyloid beta deposits are observed in the regions of the subiculum, hippocampus, and cortex at ~3 months; by ~6 months deposits become more numerous and appear in the olfactory bulb and thalamic region as well, with deposits throughout most of the forebrain by 12 months (J:89848)
• parenchymal amyloid deposits mainly present as diffuse, plaque-like deposits, with occasional deposits having a more compact structure suggesting a fibrillar nature (J:89848)
• deposits are largely in parenchyma and in diffuse form in cortex (J:124911)

immune system
• activation of microglial and astrocytes is elevated in cortex
• microglial cells show significantly increased levels of complement proteins C1q, C3 and C4

other phenotype
• mutants show decreased clearance of the mutant form of amyloid beta peptides compared to wild-type amyloid beta
• levels of amyloid beta-40 and -42 peptides are 12- and 14-fold higher in forebrain microvessels than in whole forebrain homogenates at 12 months of age; at ~3 months, levels in vasculature of forebrains is higher than whole forebrain tissue (J:89848)
• vascular amyloid beta accumulation is prominent in the thalamus and subiculum, and increases with age such that 45-55% of vessels are affected at 12 months of age; at ~6 months of age, amyloid beta deposits in and around microvessels in the thalamus and subiculum are observed (J:89848)
• microvascular amyloid beta accumulations are mainly fibrillar (J:89848)
• some arterioles in these brain regions show strong vascular and perivascular amyloid beta depostion, while blood vessel-rich regions like the hippocampal fissure show large accumulations of perivascular amyloid beta (J:89848)
• evidence of microhemorrhage is observed in microvessels with amyloid beta deposits (J:89848)
• microvascular fibrillar amyloid beta accumulation is observed in thalamic and hippocampal regions (J:124911)
• over the course of 1 year, progressive and robust accumulation of insoluble amyloid beta-40 and -42 peptides is observed in mouse brains; increase in peptides is first observed at 3 months and increases markedly by 12 months (J:89848)
• soluble and insoluble amyloid beta-40 peptide levels are 10-fold higher than amyloid beta-42 peptide levels (J:89848)
• amyloid beta deposits are observed in the regions of the subiculum, hippocampus, and cortex at ~3 months; by ~6 months deposits become more numerous and appear in the olfactory bulb and thalamic region as well, with deposits throughout most of the forebrain by 12 months (J:89848)
• parenchymal amyloid deposits mainly present as diffuse, plaque-like deposits, with occasional deposits having a more compact structure suggesting a fibrillar nature (J:89848)
• deposits are largely in parenchyma and in diffuse form in cortex (J:124911)

cardiovascular system
• reduced cerebral blood flow, CBF, response (21% increase) to whisker stimulation is observed relative to controls (38% increase) at 9 months
• with myocardin gene transfer, CBF response drops to 10% in transgenic mice, a decrease of 50%, while it increased to 27% with shSRF gene transfer compared to 19% in shGFP controls

hematopoietic system
• activation of microglial and astrocytes is elevated in cortex
• microglial cells show significantly increased levels of complement proteins C1q, C3 and C4

Mouse Models of Human Disease
OMIM IDRef(s)
Alzheimer Disease; AD 104300 J:89848
Cerebral Amyloid Angiopathy, App-Related 605714 J:89848