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 kinase Mos at high levels in the brain display progressive neuronal degeneration and gliosis. Gliosis developed in parallel with the onset of postnatal transgene expression and led to a dramatic increase in the number of astrocytes positive for GFAP, vimentin, and possibly tau. Interestingly, vimentin is normally expressed only in immature or neoplastic astrocytes, but appears to be induced to high levels in Mos-transgenic, mature astrocytes. Mos can activate mitogen activated protein kinase (MAPK) and MAPK has been implicated in Alzheimer-type tau phosphorylation. In the Mos-transgenic brain we found increased levels of phosphorylation at one epitope on tau containing serines 199 and 202 (numbering according to human tau), a pattern similar but not identical to that found in Alzheimer's disease. In addition, Mos-transgenic mice express a novel neurofilament-related protein that might be a proteolytic neurofilament heavy chain degradation product. These results suggest that activation of protein phosphorylation in neurons can result in changes in cytoskeletal proteins that might contribute to neuronal degeneration.
James
N D
ND
Ludwig Institute for Cancer Research, London, UK.
Davis
D R
DR
Sindon
J
J
Hanger
D P
DP
Brion
J P
JP
Miller
C C
CC
Rosenberg
M P
MP
Anderton
B H
BH
Propst
F
F
D000818:Animals; D001923:Brain Chemistry / Q000235:genetics; D000939:Epitopes / Q000235:genetics; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D005911:Gliosis / Q000473:pathology; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009410:Nerve Degeneration / Q000502:physiology*; D016900:Neurofilament Proteins / Q000378:metabolism*; D017232:Oncogene Proteins v-mos / Q000378:metabolism*; D010766:Phosphorylation; D012333:RNA, Messenger / Q000096:biosynthesis; D014746:Vimentin / Q000096:biosynthesis / Q000235:genetics; D016875:tau Proteins / Q000378:metabolism*
D000939:Epitopes; D005904:Glial Fibrillary Acidic Protein; D016900:Neurofilament Proteins; D017232:Oncogene Proteins v-mos; D012333:RNA, Messenger; D014746:Vimentin; D016875:tau Proteins