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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.

Type

Journal article

Journal

Neuroreport

Publication Date

20/10/1997

Volume

8

Pages

3251 - 3255

Keywords

Animals, Blotting, Western, Brain Chemistry, Calcium-Calmodulin-Dependent Protein Kinases, Glycogen Synthase Kinase 3, Glycogen Synthase Kinases, Humans, Mice, Mice, Transgenic, Mutation, Phosphorylation, Polymerase Chain Reaction, Precipitin Tests, tau Proteins