Tau phosphorylation in transgenic mice expressing glycogen synthase kinase-3beta transgenes.
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.
Brownlees
J
J
Department of Neuroscience, Institute of Psychiatry, Denmark Hill, London, UK.
Irving
N G
NG
Brion
J P
JP
Gibb
B J
BJ
Wagner
U
U
Woodgett
J
J
Miller
C C
CC
D000818:Animals; D015153:Blotting, Western; D001923:Brain Chemistry / Q000187:drug effects / Q000235:genetics; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000235:genetics / Q000378:metabolism*; D038362:Glycogen Synthase Kinase 3; D038341:Glycogen Synthase Kinases; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation; D010766:Phosphorylation; D016133:Polymerase Chain Reaction; D011233:Precipitin Tests; D016875:tau Proteins / Q000378:metabolism*
D016875:tau Proteins; D038341:Glycogen Synthase Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D038362:Glycogen Synthase Kinase 3