Disruption of cerebral cortex MET signaling in autism spectrum disorder

Daniel B. Campbell, Rosanna D'Oronzio, Krassi Garbett, Philip J. Ebert, Karoly Mirnics, Pat Levitt, Antonio M. Persico

Research output: Contribution to journalArticle

135 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)243-250
Number of pages8
JournalAnnals of Neurology
Volume62
Issue number3
DOIs
StatePublished - Sep 1 2007

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Cerebral Cortex
Hepatocyte Growth Factor
Proteins
Genes
Autism Spectrum Disorder
Messenger RNA
Brain
Receptor Protein-Tyrosine Kinases
Temporal Lobe
Reverse Transcriptase Polymerase Chain Reaction
Healthy Volunteers
Western Blotting
Alleles
RNA
DNA

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

Cite this

Campbell, D. B., D'Oronzio, R., Garbett, K., Ebert, P. J., Mirnics, K., Levitt, P., & Persico, A. M. (2007). Disruption of cerebral cortex MET signaling in autism spectrum disorder. Annals of Neurology, 62(3), 243-250. https://doi.org/10.1002/ana.21180

Disruption of cerebral cortex MET signaling in autism spectrum disorder. / Campbell, Daniel B.; D'Oronzio, Rosanna; Garbett, Krassi; Ebert, Philip J.; Mirnics, Karoly; Levitt, Pat; Persico, Antonio M.

In: Annals of Neurology, Vol. 62, No. 3, 01.09.2007, p. 243-250.

Research output: Contribution to journalArticle

Campbell, DB, D'Oronzio, R, Garbett, K, Ebert, PJ, Mirnics, K, Levitt, P & Persico, AM 2007, 'Disruption of cerebral cortex MET signaling in autism spectrum disorder', Annals of Neurology, vol. 62, no. 3, pp. 243-250. https://doi.org/10.1002/ana.21180
Campbell DB, D'Oronzio R, Garbett K, Ebert PJ, Mirnics K, Levitt P et al. Disruption of cerebral cortex MET signaling in autism spectrum disorder. Annals of Neurology. 2007 Sep 1;62(3):243-250. https://doi.org/10.1002/ana.21180
Campbell, Daniel B. ; D'Oronzio, Rosanna ; Garbett, Krassi ; Ebert, Philip J. ; Mirnics, Karoly ; Levitt, Pat ; Persico, Antonio M. / Disruption of cerebral cortex MET signaling in autism spectrum disorder. In: Annals of Neurology. 2007 ; Vol. 62, No. 3. pp. 243-250.
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