Gene networks governed by DISC-M and schizophrenia
Project/Area Number |
24591737
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Psychiatric science
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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 独立行政法人理化学研究所, 脳科学総合研究センター, チームリーダー (30249958)
|
Project Period (FY) |
2012-04-01 – 2015-03-31
|
Project Status |
Completed (Fiscal Year 2014)
|
Budget Amount *help |
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
|
Keywords | 染色体転座 / iPS細胞 / 転写因子 / 統合失調症 / 双極性障害 / 染色体異常 / 予測妥当性 / 抗精神病薬 / 扁桃体 / モデルマウス / 行動実験 / 脳波 |
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.
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Report
(4 results)
Research Products
(5 results)
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[Journal Article] Population-specific haplotype association of the postsynaptic density gene DLG4 with schizophrenia. in family-based association studies2013
Author(s)
Balan S, Yamada K, Hattori E, Iwayama Y, Toyota T, Ohnishi T, Maekawa M, Toyoshima M, Iwata Y, Suzuki K, Kikuchi M, Yoshikawa T
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Journal Title
PLoS One
Volume: 8(7)
Issue: 7
Pages: e70302-e70302
DOI
Related Report
Peer Reviewed
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[Journal Article] Lack of association of EGR2 variants with bipolar disorder in Japanese population2013
Author(s)
Balan S, Yamada K, Iwayama Y, Toyota T, Ohnishi T, Maekawa M, Toyoshima M, Iwata Y, Suzuki K, Kikuchi M, Ujike H, Inada T, Kunugi H, Ozaki N, Iwata N, Nanko S, Kato T, Yoshikawa T
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Journal Title
Gene
Volume: 526(2)
Issue: 2
Pages: 246-250
DOI
Related Report
Peer Reviewed
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