Updated 28 January 2005

General Information

Transgene:     Human longest brain tau isoform, wildtype 4 repeat tau isoform containing exons 2 and 3 as well as four microtubule-binding repeats. (human tau40 cDNA containing 115 nucleotides of 3' untranslated region subcloned into a unique XhoI site of the expression vector)

Mutation:     None

Promoter:   Neuron-specific elements of the mouse Thy.1.2 promoter

Mouse strain:   B6D2F1 x B6D2F1, founder animals were intercrossed with C57BL/6 mice to establish lines.

Phenotype

Neuropathological Analysis:

In the brain of homozygous transgenic (ALZ17 line) the level of human tau protein was approximately 1.5 fold higher than that of endogenous mouse tau.

Tau-immunoreactive nerve cells were observed in many brain regions, reactive with a number of phosphorylation-dependent anti-tau antibodies that have previously been shown to stain the neurofibrillary pathology of Alzheimer.

Prominent somatodendritic staining for hyperphosphorylated tau was observed.

Pominent axonopathy, with signs of Wallerian degeneration in distal axons, present in 3 week old Tg, with little progression up to 2 years of age.

Behavioral:

Alz17 line were unable to spread their hindlimbs when lifted by the tail.  Significant defect in motor coordination.

Availability

Patents: none

Reference

Primary:

Probst A, Gotz J, Wiederhold KH, Tolnay M, Mistl C, Jaton AL, Hong M, Ishihara T, Lee VM, Trojanowski JQ, Jakes R, Crowther RA, Spillantini MG, Burki K, Goedert M.  Axonopathy and amyotrophy in mice transgenic for human four-repeat tau protein. Acta Neuropathol (Berl) 2000 May;99(5):469-81. Abstract .

Associated:

Duff K, Knight H, Refolo LM, Sanders S, Yu X, Picciano M, Malester B, Hutton M, Adamson J, Goedert M, Burki K, Davies P. Characterization of pathology in transgenic mice over-expressing human genomic and cDNA tau transgenes. Neurobiol Dis. 7(2):87-98, 2000. Abstract