Posted 6 March 2005

General Information

Transgene: Longest human brain tau cDNA (T40) with the R406Wmutation was cloned into the mouse prion promoter (MoPrP.Xho) expression vector at the XhoI site. A 15.3 kb NotI fragment containing T40, the MoPrP promoter, together with its 3' and 5' untranslated sequences, was microinjected into fertilized C57BL6 x C3H (B6C3/F1) mouse eggs and then implanted into pseudopregnant females. Line 37 and 65 for R406W tg mice produced homozygous mice. Most experiments performed on Line37.

Mutation: Tau R406W mutation

Promoter: Mouse prion protein promoter (MoPrP)

Mouse Strain: B6C3

Phenotype

Neuropathological Analysis:

R406W tau mutation promotes the formation of filamentous tau lesions with advancing age in neuronal perikarya by a novel mechanism that may be initiated by a mutation-induced impairment of MT binding. The altered MT binding leads to retardation in the slow axonal transport of tau, followed by a cascade of events that include the perikaryal accumulation of insoluble tau to culminate in the fibrillization of tau and the formation of NFTs. Mice demonstrated neurodegeneration and a reduced lifespan.

Behavioral:

Hind leg weaknesses in older mice

Availability

Contact: Virginia M-Y Lee
The Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine
Institute on Aging, University of Pennsylvania School of Medicine, Philadelphia, PA 19104
Phone: 215-662-6427
Fax: 215-349-5909
Email: vmylee@mail.med.upenn.edu

Patents:

References

Primary:

Zhang B, Higuchi M, Yoshiyama Y, Ishihara T, Forman M S, Martinez D, Joyce S, Trojanowski J Q, Lee V M-Y. Retarded Axonal Transport of R406W Mutant Tau in Transgenic Mice with a Neurodegenerative Tauopathy. J Neurosci. 24(19):4657-4667, 2004. Abstract.