TAU-PHOSPHORYLATION IN TRANSGENIC MICE EXPRESSING GLYCOGEN-SYNTHASE KINASE-3-BETA TRANSGENES

IN order to investigate the effect on tau of manipulating glycogen syn thase kinase (GSK)-3 beta activity in the brain, we created transgenic mice harbouring wild-type GSK-3 beta genes or a mutant GSK-3 beta tha t is predicted to be more active. Transgene-derived mRNAs were detecte d in the brains of a number of the transgenic mouse lines and several of these transgenic lines displayed transgenic GSK-3 beta activity. We stern blot analyses of the two lines with the highest levels of transg enic GSK-3 beta activity revealed that the phosphorylation status of t au was elevated at the AT8 epitope. These observations strongly sugges t that GSK-3 beta is an in vivo tau kinase in the brain. Only low leve ls of expression of GSK-3 beta were obtained and it is possible that h igh levels of GSK-3 beta activity are lethal.