Updated 28 January 2005

Transgene:

Mouse Pin1 gene comprising a 997bp fragment upstream of first coding exon and a 6.5 fragment downstream of last exon was inserted into pLNTK carrying the neomycin resistance, thymidine kinase and Lox-P genes.

Background: Backcross to C57BL/6, N 11

Phenotype

Neuropathological analysis:

Progressive age-dependent neuropathy: tau hyperphosphorylation, tau filament formation and neuronal degeneration. Pin1^-/- neurons have NFT-like pathologies. Total MPM-2 reactivity was 3x higher in Pin1^-/- brain lysates compared to control brain lysates.

Behavioral:

Normal development but showed progressive age-dependent motor and behavioral deficits, including abnormal limb-clasping reflexes, hunched postures, reduced mobility and eye irritation.

Availability:

Takafumi Uchida
Center for Interdisciplinary Research/Institute of Development, Aging and Cancer
Aramaki Aza-Aoba, Aoba, Sendai, 980-8578 Japan.
Phone: 81-22-217-5759
Fax: 81-22-217-5759
Email: uchidat@idac.tohoku.ac.jp

Reference

Primary:

Fujimori F, Takahashi K,Uchida C, Uchida T. Mice Lacking Pin1 Develop Normally, but Are Defective in Entering Cell Cycle from G0 Arrest. Biochm Biophy Res Comm 265:658-663, 1999.

Associated:

Y.C. Liou, R. Ryo, H.K. Huang, P.J. Lu, R. Bronson, F. Fujimori, U. UchidaÞ, T. Hunter and K.P. Lu, Loss of Pin1 function in the mouse causes phenotypes resembling cyclin D1-null phenotypes, Proc. Natl. Acad. Sci. USA. 99:1335-1340, 2002. Abstract

Liou Y-C, Sun A, Ryo A, Zhou X Z, Yu Z-X, Huang H-K, Uchida T, Bronson R, Bing G, Li X, Hunter T & Lu K P. Role of the prolyl isomerase Pin1 in protecting against age-dependent neurodegeneration. Nature 424, 556 - 561, 2003. Abstract