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

SCHIZOPHRENIA RESEARCH

卷:130

Article

Katsel, Pavel¹  Tan, Weilun¹  Abazyan, Bagrat^3,4,5  Davis, Kenneth L.¹  Ross, Christopher^3,4,5  Pletnikov, Mikhail V.^3,4,5  Haroutunian, Vahram^1,2 

[1] Mt Sinai Sch Med, Dept Psychiat, New York, NY 10029 USA

[2] James J Peters VA Med Ctr, Dept Psychiat, Bronx, NY 10468 USA

[3] Johns Hopkins Univ, Sch Med, Dept Psychiat, Baltimore, MD 21205 USA

[4] Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA

[5] Johns Hopkins Univ, Sch Med, Dept Mol & Comparat Parhobiol, Baltimore, MD USA

关键词: Schizophrenia;    Disrupted-in schizophrenia 1;    Gene expression;    Oligodendrocyte;    Oligodendrogenesis;    Myelin;    Neuregulin;   

DOI  :  10.1016/j.schres.2011.04.021

来源: Elsevier

【 摘 要 】

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 (DISCI) in neural development. Transgenic mice with forebrain restricted expression of mutant human DISC1 (Delta hDISC1) are characterized by neuroanatomical and behavioral abnormalities reminiscent of some features of SZ. We sought to determine whether the expression of Delta hDISC1 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 Delta hDISC1 mice during different stages of neurodevelopment (E15 and P1 days) and in adulthood. The results suggest that the expression of Delta hDISC1 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. (C) 2011 Elsevier B.V. All rights reserved.

【 授权许可】

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