General Terms and Conditions

Related Disease (OMIM) Terms

Alzheimer Disease; AD

Mammalian Phenotype Terms assigned by genotype

Tg(Thy1-APPSwDutIowa)BWevn/0

        involves: C57BL/6

• nervous system phenotype
• abnormal astrocyte morphology (MGI Ref ID J:124911)
  • astrocyte numbers and density are enhanced in thalamic and cortical regions where fibrillar amyloid beta deposits are prominent
• abnormal microglial cell physiology (MGI Ref ID J:124911)
  • activation of microglial and astrocytes is elevated in cortex
  • microglial cells show significantly increased levels of complement proteins C1q, C3 and C4
• amyloid beta deposits (MGI Ref ID J:89848)
  • 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
  • soluble and insoluble amyloid beta-40 peptide levels are 10-fold higher than amyloid beta-42 peptide levels
  • 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
  • parenchymal amyloid deposits mainly present as diffuse, plaque-like deposits, with occasional deposits having a more compact structure suggesting a fibrillar nature
  • deposits are largely in parenchyma and in diffuse form in cortex
• cerebral amyloid angiopathy (MGI Ref ID J:89848)
  • 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
  • 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
  • microvascular amyloid beta accumulations are mainly fibrillar
  • 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
  • evidence of microhemorrhage is observed in microvessels with amyloid beta deposits
  • microvascular fibrillar amyloid beta accumulation is observed in thalamic and hippocampal regions
• immune system phenotype
• abnormal complement physiology (MGI Ref ID J:124911)
  • in thalamus, hippocampus and subiculum, increased levels of 3 early complement components C1q, C3, and C4, are detected compared to control animals
  • increased levels of synthesis of complement proteins is found in cortical and thalamic regions of transgenic brains
• abnormal microglial cell physiology (MGI Ref ID J:124911)
  • activation of microglial and astrocytes is elevated in cortex
  • microglial cells show significantly increased levels of complement proteins C1q, C3 and C4
• other phenotype
• amyloidosis (MGI Ref ID J:89848)
  • mutants show decreased clearance of the mutant form of amyloid beta peptides compared to wild-type amyloid beta
• amyloid beta deposits (MGI Ref ID J:89848)
  • 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
  • soluble and insoluble amyloid beta-40 peptide levels are 10-fold higher than amyloid beta-42 peptide levels
  • 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
  • parenchymal amyloid deposits mainly present as diffuse, plaque-like deposits, with occasional deposits having a more compact structure suggesting a fibrillar nature
  • deposits are largely in parenchyma and in diffuse form in cortex
• cerebral amyloid angiopathy (MGI Ref ID J:89848)
  • 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
  • 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
  • microvascular amyloid beta accumulations are mainly fibrillar
  • 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
  • evidence of microhemorrhage is observed in microvessels with amyloid beta deposits
  • microvascular fibrillar amyloid beta accumulation is observed in thalamic and hippocampal regions
• cardiovascular system phenotype
• abnormal blood circulation (MGI Ref ID J:119251)
  • 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