2017 Fiscal Year Final Research Report
Exploration of the causative genes and elucidation of the pathophysiology on immune dysregulatory diseases with intractable inflammation
| Project/Area Number |
15H04876
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Pediatrics
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| Research Institution | Kyoto University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
八角 高裕 京都大学, 医学研究科, 講師 (00511891)
平家 俊男 京都大学, 医学研究科, 名誉教授 (90190173)
斎藤 潤 京都大学, iPS細胞研究所, 准教授 (90535486)
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| Co-Investigator(Renkei-kenkyūsha) |
OHARA Osamu かずさDNA研究所, ヒトゲノム研究部, 部長 (20370926)
TOGUCHIDA Junya 京都大学, iPS細胞研究所, 教授 (40273502)
FUJITA Takashi 京都大学, ウイルス研究所, 教授 (10156870)
KATO Hiroki 京都大学, ウイルス研究所, 准教授 (10597173)
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| Research Collaborator |
TANAKA Takayuki
NAKAGAWA Kenji
HONDA Yoshitaka
SHIMODERA Saeko
OHTO Taisuke
ODA Hirotsugu
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| Project Period (FY) |
2015-04-01 – 2018-03-31
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| Keywords | NLRC4異常症 / FLNA異常症 / iPS細胞 / 全エクソーム解析 / メバロン酸キナーゼ欠損症 / Aicardi-Goutieres症候群 / 炎症性疾患 / 原発性免疫不全症 |
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| Outline of Final Research Achievements |
To identify the responsible gene for the intractable inflammatory diseases, we performed genomic analysis including whole exome-sequencing. In addition, we utilized disease-specific iPS cells as well as gene-targeted mouse models to delineate the pathophysiology of the inflammatory diseases. First, we identified NLRC4 gene as a new responsible gene for the CINCA/NOMID. In particular, we demonstrated the identified NLRC4 variant was disease-causing by genetic modification of iPS cells by CRISPR/Cas9 system. We also diagnosed FLNA deficiency on the 2 brothers suffering from inflammatory bowel diseases, valvulopathy, malrotation of intestine, and chronic intestinal pseudo-obstruction. We created and studied knock-in mice for mevalonate kinase deficiency and BAC transgenic mice for Aicardi-Goutieres syndrome.
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| Free Research Field |
小児科学
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