Regulation of a novel alphaN-catenin splice variant in schizophrenic smokers

Am J Med Genet B Neuropsychiatr Genet. 2008 Sep 5;147B(6):759-68. doi: 10.1002/ajmg.b.30679.

Abstract

The alphaN-catenin (CTNNA2) gene represents a promising candidate gene for schizophrenia based upon previous genetic linkage, expression, and mouse knockout studies. CTNNA2 is differentially regulated by smoking in schizophrenic patients. In this report, the genomic structure of a primate-specific alphaN-catenin splice variant (alphaN-catenin III) is described. A comparison of alphaN-catenin III mRNA expression across postmortem hippocampi from schizophrenic and non-mentally ill smokers and non-smokers revealed a significant decrease in expression among patient non-smokers compared to all other groups. The recent evolutionary divergence of this gene, as well as the differences in gene expression in postmortem brain of schizophrenic non-smokers, supports the role of alphaN-catenin III as a novel disease susceptibility gene.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adult
  • Aged
  • Alternative Splicing / physiology
  • Amino Acid Sequence
  • Base Sequence
  • Chromosomes, Human, Pair 2
  • Female
  • Gene Expression Regulation*
  • Genetic Linkage
  • Hippocampus / metabolism
  • Hippocampus / pathology
  • Humans
  • Male
  • Middle Aged
  • Molecular Sequence Data
  • Nerve Tissue Proteins / genetics*
  • Nerve Tissue Proteins / isolation & purification
  • Nerve Tissue Proteins / metabolism
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism
  • Schizophrenia / complications
  • Schizophrenia / genetics*
  • Schizophrenia / metabolism
  • Schizophrenia / pathology
  • Sequence Homology
  • Smoking / genetics*
  • Smoking / metabolism
  • Smoking / pathology
  • alpha Catenin / genetics*
  • alpha Catenin / isolation & purification
  • alpha Catenin / metabolism

Substances

  • Ctnna2 protein, mouse
  • Nerve Tissue Proteins
  • Protein Isoforms
  • alpha Catenin