RESEARCH: MSA Mouse Model Discovered

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For the layman's article on this discovery see this website:

http://unisci.com/stories/20022/0610025.htm

Regards,

Pam

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EMBO Rep 2002 Jun;3(6):583-588

Hyperphosphorylation and insolubility of {alpha}-synuclein in transgenic

mouse

oligodendrocytes.

Kahle PJ, Neumann M, Ozmen L, Muller V, sen H, Spooren W, Fuss B,

Mallon B,

Macklin WB, Fujiwara H, Hasegawa M, Iwatsubo T, Kretzschmar HA, Haass C.

1Laboratory for Alzheimer's and Parkinson's Disease Research, Department of

Biochemistry, Ludwig Maximilians University, D-80336 Munich, 2Department of

Neuropathology, Ludwig Maximilians University, D-81377 Munich, Germany,

3Pharma

Research, F. Hoffmann-La Roche Ltd, CH-4002 Basel, Switzerland, 4Department

of

Neurosciences, Lerner Research Institute, Cleveland Clinic Foundation,

Cleveland, OH 44195, USA and 5Department of Neuropathology and Neuroscience,

Graduate School of Pharmaceutical Sciences, University of Tokyo, Tokyo

113-0033,

Japan.

(Oligodendro)glial cytoplasmic inclusions composed of alpha-synuclein

(alphaSYN)

characterize multiple system atrophy (MSA). Mature oligodendrocytes (OLs) do

not

normally express alphaSYN, so MSA pathology may arise from aberrant

expression

of alphaSYN in OLs. To study pathological deposition of alphaSYN in OLs,

transgenic mice were generated in which human wild-type alphaSYN was driven

by a

proteolipid protein promoter. Transgenic alphaSYN was detected in OLs but no

other brain cell type. At the light microscopic level, the transgenic

alphaSYN

profiles resembled glial cytoplasmic inclusions. Strikingly, the diagnostic

hyperphosphorylation at S129 of alphaSYN was reproduced in the transgenic

mice.

A significant proportion of the transgenic alphaSYN was detergent insoluble,

as

in MSA patients. The histological and biochemical abnormalities were

specific

for the disease-relevant alphaSYN because control green fluorescent protein

was

fully soluble and evenly distributed throughout OL cell bodies and

processes.

Thus, ectopic expression alphaSYN in OLs might initiate salient features of

MSA

pathology.

PMID: 12034752 [PubMed - as supplied by publisher]

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