NEURODEGENERATIVE CHANGES INCLUDING ALTERED TAU-PHOSPHORYLATION AND NEUROFILAMENT IMMUNOREACTIVITY IN MICE TRANSGENIC FOR THE SERINE THREONINE KINASE MOS

Transgenic mice expressing the oncogenic protein-serine/threonine kina se Mos at high levels in the brain display progressive neuronal degene ration and gliosis. Gliosis developed in parallel with the onset of po stnatal transgene expression and led to a dramatic increase in the num ber of astrocytes positive for GFAP, vimentin, and possibly tau. Inter estingly, vimentin is normally expressed only in immature or neoplasti c astrocytes, but appears to be induced to high levels in Mos-transgen ic, mature astrocytes. Mos can activate mitogen activated protein kina se (MAPK) and MAPK has been implicated in Alzheimer-type tau phosphory lation. In the Mos-transgenic brain we found increased levels of phosp horylation at one epitope on tau containing serines 199 and 202 (numbe ring according to human tau), a pattern similar but not identical to t hat found in Alzheimer's disease. In addition, Mos-transgenic mice exp ress a novel neurofilament-relate protein that might be a proteolytic neurofilament heavy chain degradation product. These results suggest t hat activation of protein phosphorylation in neurons can result in cha nges in cytoskeletal proteins that might contribute to neuronal degene ration.