Phenotypes Associated with This Genotype

Genotype
MGI:4940110

• Allelic Composition: Mapt^tm1(EGFP)Klt/Mapt^tm1(EGFP)Klt; Tg(Thy1-MAPT*)30Schd/0
• Genetic Background: involves: 129S4/SvJae * C57BL/6 * CBA

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

mortality/aging

premature death ( J:169074 )

• mice show reduced survival relative to wild-type, with almost 100% mortality observed by 16 months

• accelerated mortality is observed before 3 months of age (after 1 month of age) compared to wild-type or Tg(Thy1-MAPT*)30Schd single mutant animals

nervous system

nervous system phenotype ( J:169074 )

N • at 12 months, neuronal cell numbers are similar in the hippocampal CA1-CA3 sectors and spinal cord to those in Tg(Thy1-MAPT*)30Schd mice; volumes of brain, cortex, hippocampal formation and cervical spinal cord are similar

abnormal brain morphology ( J:169074 )

• mice show significantly increased proportion of insoluble tau protein relative to sarkosyl-soluble tau compared to Tg(Thy1-MAPT*)30Schd single mutants

• soluble tau shows decreased phosphorylation compared to single transgenics, while insoluble tau displays significantly elevated phosporylation levels

• GSK-3 kinase activation in the brain is increased compared to wild-type and single mutants

neurofibrillary tangles ( J:169074 )

• NFTs are detected in the hippocampus, cortex, subcortical areas, brainstem, and spinal cord at 12 months, while no tangles are found in wild-type or Mapt mutants

• density (number) of NFTs is significantly increased in the hippocampus (subiculum and CA1 region) compared to Tg(Thy1-MAPT*)30Schd single mutants, but is similar between lines in the spinal cord

abnormal sciatic nerve morphology ( J:169074 )

• mice display axonal loss and reduction in cross-sectional area and axon density in the sciatic nerve compared to wild-type or Mapt mutants

abnormal spinal cord morphology ( J:169074 )

• mice develop numerous pericaryal rounded inclusions in the spinal cord; these are composed to abnormal filaments mixed with abundant neurofilaments; these are more numerous than seen in single transgenics

behavior/neurological

behavior/neurological phenotype ( J:169074 )

N • in Y-maze tests, percentage of alternations observed is not significantly different from single transgenics, Mapt mutants or wild-type at 3-6 months of age

impaired coordination ( J:169074 )

• mice show a progressive motor deficit, significant from 6 to 12 months compared to wild-type or Mapt mutants; impairment is much more severe than in Tg(Thy1-MAPT*)30Schd single mutants