another: Met tyrosine cortex autism ASDs

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Ann Neurol. 2007 Sep;62(3):243-50.

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<http://www.ncbi.nlm.nih.gov/entrez/utils/fref.fcgi?PrId=3058 & itool=AbstractPlus\

-def & uid=17696172 & db=pubmed & url=http://dx.doi.org/10.1002/ana.21180>

Disruption of cerebral cortex MET signaling in autism spectrum

disorder.

DB, D'Oronzio R, Garbett K, Ebert PJ, Mirnics K, Levitt P,

Persico AM.

OBJECTIVE: Multiple genes contribute to autism spectrum disorder

(ASD) susceptibility. One particularly promising candidate is the

MET gene, which encodes a receptor tyrosine kinase that mediates

hepatocyte growth factor (HGF) signaling in brain circuit formation,

immune function, and gastrointestinal repair. The MET promoter

variant rs1858830 allele " C " is strongly associated with ASD and

results in reduced gene transcription. Here we examined expression

levels of MET and members of the MET signaling pathway in postmortem

cerebral cortex from ASD cases and healthy control subjects.

METHODS: Protein, total RNA, and DNA were extracted from postmortem

temporal cortex gray matter samples (BA 41/42, 52, or 22) belonging

to eight pairs of ASD cases and matched control subjects. MET

protein expression was determined by Western blotting; messenger RNA

expression of MET and other related transcripts was assayed by

microarray and quantitative reverse transcriptase polymerase chain

reaction. RESULTS: MET protein levels were significantly decreased

in ASD cases compared with control subjects. This was accompanied in

ASD brains by increased messenger RNA expression for proteins

involved in regulating MET signaling activity. Analyses of

coexpression of MET and HGF demonstrated a positive correlation in

control subjects that was disrupted in ASD cases. INTERPRETATION:

Altered expression of MET and related molecules suggests

dysregulation of signaling that may contribute to altered circuit

formation and function in ASD. The complement of genes that encode

proteins involved in MET activation appears to undergo long-term

compensatory changes in expression that may be a hallmark

contribution to the pathophysiology of ASD.

PMID: 17696172