Expression of mutant human DISC1 in mice supports abnormalities in differentiation of oligodendrocytes

Pavel Katsel, Weilun Tan, Bagrat Abazyan, Kenneth L. Davis, Christopher Ross, Mikhail V. Pletnikov, Vahram Haroutunian

Research output: Contribution to journalArticlepeer-review

Abstract

Abnormalities in oligodendrocyte (OLG) differentiation and OLG gene expression deficit have been described in schizophrenia (SZ). Recent studies revealed a critical requirement for Disrupted-in-Schizophrenia 1 (DISC1) in neural development. Transgenic mice with forebrain restricted expression of mutant human DISC1 (δhDISC1) are characterized by neuroanatomical and behavioral abnormalities reminiscent of some features of SZ. We sought to determine whether the expression of δhDISC1 may influence the development of OLGs in this mouse model.OLG- and cell cycle-associated gene and protein expression were characterized in the forebrain of δhDISC1 mice during different stages of neurodevelopment (E15 and P1 days) and in adulthood.The results suggest that the expression of δhDISC1 exerts a significant influence on oligodendrocyte differentiation and function, evidenced by premature OLG differentiation and increased proliferation of their progenitors. Additional findings showed that neuregulin 1 and its receptors may be contributing factors to the observed upregulation of OLG genes.Thus, OLG function may be perturbed by mutant hDISC1 in a model system that provides new avenues for studying aspects of the pathogenesis of SZ.

Original languageEnglish (US)
Pages (from-to)238-249
Number of pages12
JournalSchizophrenia Research
Volume130
Issue number1-3
DOIs
StatePublished - Aug 2011

Keywords

  • Disrupted-in schizophrenia 1
  • Gene expression
  • Myelin
  • Neuregulin
  • Oligodendrocyte
  • Oligodendrogenesis
  • Schizophrenia

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Biological Psychiatry

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