Tau phosphorylation in transgenic mice expressing glycogen synthase kinase-3beta transgenes.

Journal article

In order to investigate the effect on tau of manipulating glycogen synthase kinase (GSK)-3beta activity in the brain, we created transgenic mice harbouring wild-type GSK-3beta genes or a mutant GSK-3beta that is predicted to be more active. Transgene-derived mRNAs were detected in the brains of a number of the transgenic mouse lines and several of these transgenic lines displayed transgenic GSK-3beta activity. Western blot analyses of the two lines with the highest levels of transgenic GSK-3beta activity revealed that the phosphorylation status of tau was elevated at the AT8 epitope. These observations strongly suggest that GSK-3beta is an in vivo tau kinase in the brain. Only low levels of expression of GSK-3beta were obtained and it is possible that high levels of GSK-3beta activity are lethal.

Authors: Brownlees, J; Irving, N; Brion, J; Gibb, B; Wagner, U

• Publication status: Published
• Journal: Neuroreport
• Volume: 8
• Issue: 15
• Pages: 3251-3255
• Publication date: 1997-10-01
• DOI: 10.1097/00001756-199710200-00013
• EISSN: 1473-558X
• ISSN: 0959-4965
• Language: English
• Keywords: Phosphorylation; Calcium-Calmodulin-Dependent Protein Kinases; Glycogen Synthase Kinase 3; Mice; Glycogen Synthase Kinases; Mutation; Humans; Precipitin Tests; Polymerase Chain Reaction; Animals; Blotting, Western; Brain Chemistry; tau Proteins; Mice, Transgenic