Gene networks governed by DISC-M and schizophrenia

2014 Fiscal Year Final Research Report

• Project/Area Number: 24591737
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Psychiatric science
• Research Institution: The Institute of Physical and Chemical Research
• Principal Investigator: OHNISHI TETSUO 独立行政法人理化学研究所, 脳科学総合研究センター, 研究員 (80373281)
• Co-Investigator(Kenkyū-buntansha): YOSHIKAWA Takeo (30249958)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: 染色体転座 / iPS細胞 / 転写因子

Outline of Final Research Achievements

We focused on a schizophrenia case with a balanced chromosomal translocation. We determined the precise structure of the patient's genome. We found the DISC-M is a gene that is the most proximal to the breakpoint within chr.4. In cells from the patient, the expression of DISC-M was significantly unregulated. We confirmed that the DISC-M gene product forms various transcription complexes by co-immunoprecipitation assay, regulating the expressions of multiple genes in the brain. Rare mutations that were found in bipolar patients did not affect the efficiency of the protein complex formation. Interestingly, those two mutations appeared to stabilize the DISC-M protein in the cells.
In conclusion, DISC-M support normal brain development by regulating the expressions of downstream genes, and the dysfunction of the gene and gene networks governed by DISC-M might form a predisposition to mental disorders such as schizophrenia and bipolar disorder.

Free Research Field

神経科学