| Project/Area Number |
24659143
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Single-year Grants |
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| Research Field |
Pathological medical chemistry
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| Research Institution | Chiba University |
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Principal Investigator |
KITAGAWA Motoo 千葉大学, 医学(系)研究科(研究院), 准教授 (40262026)
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| Co-Investigator(Kenkyū-buntansha) |
TANIGAKI Kenji 滋賀県立成人病センター, 研究員 (70362473)
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| Co-Investigator(Renkei-kenkyūsha) |
HASHIMOTO Kenji 千葉大学, 社会精神保健教育研究センター, 教授 (10189483)
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| Project Period (FY) |
2012-04-01 – 2014-03-31
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| Project Status |
Completed (Fiscal Year 2013)
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| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2012: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | Notchシグナル / 統合失調症 / Mastermind |
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| Research Abstract |
During Notch signaling, ligand stimulation induces generation of Notch intracellular domain, which is subsequently transported to the nuclei. With a DNA-binding protein RBP-J and a transcriptional co-activator Mastermind (Mam), the Notch intracellular domain forms a trimeric complex that activates transcription from the target promoters. We had found that heterozygous knockout mice of one of Mam genes, MamL1, exhibit increased sensitivity to dopamine, mimicking a part of symptoms of schizophrenia in humans. We have found heterozygous knockout mice of Rbp-j also exhibit very similar phenotype. Furthermore, by examining blood-derived genomic DNA from schizophrenic patients and healthy controls, we have found schizophrenia-specific missense polymorphisms in coding regions of both RBP-J and MAML1 genes. We are examining effects of these polymorphisms on the functions of these proteins.
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