| Project/Area Number |
15H04699
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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 |
General medical chemistry
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| Research Institution | Osaka University |
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Principal Investigator |
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| Research Collaborator |
SHIROMOTO Yusuke
NISHIMURA Tohru
NAGAMORI Ippei
ASADA Noriko
NAKANO Toru
TOMARI Yukihide 東京大学, 分子生物学研究所
IZUMI Natsuko 東京大学, 分子生物学研究所
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| Project Period (FY) |
2015-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥17,030,000 (Direct Cost: ¥13,100,000、Indirect Cost: ¥3,930,000)
Fiscal Year 2017: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Fiscal Year 2016: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2015: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
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| Keywords | piRNA / 小分子RNA / 精子形成 / レトロトランスポゾン / 生殖顆粒 / GPAT2 / PIWI / PNLDC1 / piRNA合成 / ミトコンドリア / 発生・分化 / piRNA生合成 |
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| Outline of Final Research Achievements |
piRNAs are germ cell-specific small RNAs essential for retrotransposon gene silencing and male germ cell development. We generated GPAT2-deficient and PNLDC1-deficient mice. Each deficient mice showed the complete loss of piRNAs in GPAT2-deficient, and accumulation of longer piRNAs in PNLDC1-deficient, suggesting PNLDC1 as a candidate pre-piRNA trimming enzyme in mice, respectively. Apoptosis of pachytene spermatocytes was observed in GPAT2-deficient testis. In addition, apoptosis of spermatogonia at the neonatal stage, which was not observed in other piRNA impaired mice. These data show that GPAT2 plays a critical role in preventing apoptosis in spermatogonia, as well as piRNA production. On the other hand, male germ cells in the PNLDC1-mutant mouse lines showed two types of apoptosis, at the meiotic and post-meiotic stages. These abnormalities can be attributed to the trimming deficiency in both embryonic and postnatal piRNA production.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究は、生殖細胞に存在し、piRNAの生合成にかかわる分子の生体内における役割を、欠損マウスを作製して解析したものである。PNLDC1欠損マウスの解析では、piRNAが数塩基削られること（トリミング）による成熟化が、精子形成にどのような影響があるかをあきらかにした重要な研究である。また、ミトコンドリア外膜タンパクであるGPAT2は、piRNAの生合成に必須であるだけでなく、雄性生殖幹細胞の増殖にも重要な役割を果たしている可能性が示唆された。
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