Molecular NeuroscienceTau phosphorylation in transgenic mice expressing glycogen synthase kinase-3β transgenesBrownlees, Janet1; Irving, Nicholas G.1; Brion, Jean-Pierre2; M. Gibb, Barry J.1; Wagner, Uta1; Woodgett, James3; J. Miller, Christopher C.1,4Author Information 1Departments of Neuroscience, Clinical Neurosciences and Psychology, Institute of Psychiatry, De Crespigny Park, Denmark Hill, London SE5 8AF, UK 2Université Libre de Bruxelles, Campus Erasme Bldg C-10, Laboratoire D'Anatomie et de Microscopie Electronique, 808 Route De Lennik, B-1070, Bruxelles, Belgium 3Ontario Cancer Research Institute/Princess Margaret Hospital, 610 University Avenue, Toronto, Ontario M5G 2M9, Canada 4Corresponding Author: Christopher C. J. Miller ACKNOWLEDGEMENTS: We thank Don Cleveland for the NF-L gene, Fritz Propst for the MSV promoter and Brian Anderton for support and advice and for critical reading of the manuscript. This work was supported by grants from the Wellcome Trust, MRC, Nuffield Foundation, a European Neuroscience grant and a donation from BAT. Website publication 29 September 1997 Received 3 July 1997; accepted 9 August 1997 NeuroReport: October 20th, 1997 - Volume 8 - Issue 15 - p 3251-3255 Buy Abstract IN order to investigate the effect on tau of manipulating glycogen synthase kinase (GSK)-3β activity in the brain, we created transgenic mice harbouring wild-type GSK-3β genes or a mutant GSK-3β 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-3β activity. Western blot analyses of the two lines with the highest levels of transgenic GSK-3β activity revealed that the phosphorylation status of tau was elevated at the AT8 epitope. These observations strongly suggest that GSK-3β is an in vivo tau kinase in the brain. Only low levels of expression of GSK-3β were obtained and it is possible that high levels of GSK-3β activity are lethal. © Lippincott-Raven Publishers.