Characterization of pathology in transgenic mice over-expressing human genomic and cDNA tau transgenes

To examine the normal cellular function of tau and its role in pathogenesis , we have created transgenic mice that overexpress a tau transgene derived from a human PAC that contains the coding sequence, intronic regions, and r egulatory regions of the human gene. All six isoforms of human tau are repr esented in the transgenic mouse brain at the mRNA and protein level and the human tau is distributed in neurites and at synapses, but is absent from c ell bodies. A comparison between the genomic tau mice and mice that overexp ress a tau cDNA transgene shows that overall, the distribution of tau is si milar in the two lines, but human tau is located in the somatodendritic com partment of many neurons in the cDNA mice. Tau-immunoreactive axonal swelli ngs were found in the spinal cords of the cDNA mice, which correlated with a hind-limb abnormality, whereas neuropathology was essentially normal in t he genomic mice up to 8 months of age. (C) 2000 Academic Press.