| Project/Area Number |
17K19738
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| Research Category |
Grant-in-Aid for Challenging Research (Exploratory)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Surgery related to the biological and sensory functions and related fields
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| Research Institution | National Center for Child Health and Development |
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Principal Investigator |
Matsuzaka Emiko 国立研究開発法人国立成育医療研究センター, 視覚科学研究室, 研究補助員 (70789974)
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| Research Collaborator |
AZUMA noriyuki
FUKAMI maki
TAKADA shuji
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| Project Period (FY) |
2017-06-30 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2018: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2017: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
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| Keywords | 第一硝子体過形成遺残 / エクソーム解析 / CRISPR/Cas9 / 遺伝子改変マウス / 第一次硝子体過形成遺残 / 遺伝子解析 / ゲノム解析 / 疾患iPS |
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| Outline of Final Research Achievements |
We have identified a large pedigree of congenital ocular disease, persistent fetal vasculature (PFV), with autosomal dominant inheritance. Whole exome analysis revealed a functionally unknown gene X as a possible causative gene of the disease, and we generated knockout mice of this gene by CRISPR/Cas9 system.
Heterozygous knockout mice of exon2 showed eye phenotype resembling PFV observed in the pedigree, while homozygous knockout mice of exon2 were lethal. Homozygous knockout mice of exon6 were not lethal, however, the mice showed minute eye phenotype. In order to identify the effect of the gene X for the other organs, we have conducted the generation of another homozygous knockout mice carrying mutation in exon3 or exon4. As a result, heterozygous knockout mice of exon3 have been lethal, while the heterozygous knockout mice of exon4 have not been lethal. We further aim to generate homozygous knockout mice of exon4 which show eye and systemic phenotype.
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| Academic Significance and Societal Importance of the Research Achievements |
国立成育医療センター眼科には小児の遺伝性眼疾患症例が全国から集積されており、第一硝子体過形成遺残のみならず、他の遺伝性網膜疾患においても膨大な臨床、遺伝学的データが蓄積されており、今後同様に研究を進めることで新たな遺伝子変異を同定し疾患治療に結びつく可能性がある。
同様に、他の疾患についても遺伝学的、また分子生物学的に解析を進めることで、網膜・視神経の発生に関わる知見のみならず、眼形成初期に働く遺伝子であり、かつ身体の発育を司る遺伝子を新規に同定できる可能性がある。
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