2019 Fiscal Year Final Research Report
C. elegans as a new disease model of human glycodiseases
| Project/Area Number |
16K07298
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Functional biochemistry
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| Research Institution | Kurume University (2018-2019)
Kyushu University (2016-2017) |
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Principal Investigator |
Nomura Kazuya 久留米大学, 医学部, 准教授 (30150395)
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| Co-Investigator(Kenkyū-buntansha) |
山本 健 久留米大学, 医学部, 教授 (60274528)
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| Project Period (FY) |
2016-04-01 – 2020-03-31
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| Keywords | 先天性グリコシル化異常症 / 糖鎖遺伝子 / 不妊 / O157 / 志賀毒素 / GPIアンカー / 配偶子幹細胞 / アセチルCoAトランスポーター |
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| Outline of Final Research Achievements |
By using the nematode C. elegans as a model of various glycodiseases, we found that the key enzyme of N-glycosylation (DPAGT1) plays essential roles in oogenesis and development, and clarified molecular mechanisms of causing abnormalities by RNAi. We also found that GPI-anchored proteins expressed in the germline stem cell niche are involved in germline stem cell proliferation and are important for germline formation. Molecular mechanisms of the genes in germline formation were also clarified by RNAi. By making use of a humanized C. elegans expressing Shiga toxin receptor Gb3 in intestinal cells, we found that infection of the toxin results in over expression of neuronal specific genes, and we found that the orthologs of the nematode genes are also highly expressed in patients of O157. This line of study is underway in my collaborator's laboratory. In addition, we showed that the nematode can be used as a useful model of human acetyl CoA transported defected patients.
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| Free Research Field |
糖鎖生物学
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| Academic Significance and Societal Importance of the Research Achievements |
線虫C. elegansがヒトの先天性グリコシル化異常症CGDの強力なモデルシステムであることを示し、特にDPAGT1やGPIアンカー型タンパク質が卵母細胞形成や配偶子幹細胞形成に不可欠であることを発見した。これは従来見逃されていた多くの不妊症の原因遺伝子としてこうした糖鎖遺伝子が潜んでいることを示しており今後、重要な診断項目となることが期待される。またO157感染症の線虫モデルが、ヒトのO157感染ときわめて類似した遺伝子発現パターン変化を示す事や、アセチルCoAトランスポーター遺伝子破壊がヒトの同遺伝子異常の良いモデルとなることの発見は今後の線虫を用いた疾病研究の有効性を如実に示している。
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