2019 Fiscal Year Research-status Report
Discovery of genes essential for male fertility using CRISPR/Cas9-based genome editing technology
| Project/Area Number |
18K16735
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| Research Institution | Osaka University |
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Principal Investigator |
Lu Yonggang 大阪大学, 微生物病研究所, 特任研究員(常勤) (00817033)
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| Project Period (FY) |
2018-04-01 – 2022-03-31
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| Keywords | male reproduction / male contraception / sperm function / sperm-oocyte fusion |
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| Outline of Annual Research Achievements |
Using the CRISPR/Cas9 genome editing system, I generated multiple knockout mouse lines to interrogate the essentiality of target genes in male reproduction.
The knockout male mice that show normal fecundity have been summarized and published in an internationally peer-reviewed journal, Biology of Reproduction. Another paper reporting more than 10 non-essential male genes is under revision and will be published soon. Since such functionally redundant genes are of diminished biological and clinical significance, it is crucial to disseminate the genes to the scientific community, along with their phenotypic information, to avoid unnecessary expenditure of time and research funds and duplication of efforts by other labs.
Another paper depicting novel sperm genes that are required for sperm-oocyte fusion has been published recently in PNAS. The fusion-related genes Spaca6 and Tmem95 were knocked out during my initial screening. Knockout sperm can penetrate the zona pellucida of mouse oocytes but cannot fuse with the oocyte plasma membrane. However, the well-known fusion-required sperm protein IZUMO1, which was also reported by our lab, was found to express and behave normally in Spaca6 or Tmem95 knockout sperm, suggesting SPACA6 and TMEM95 may be participate in sperm-oocyte fusion in an IZUMO1-independent manner. The discovery of new fusion-related molecules would facilitate the understanding of this key reproductive event.
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| Current Status of Research Progress |
Current Status of Research Progress
1: Research has progressed more than it was originally planned.
Reason
The discovery of many male genes essential for reproduction during the initial screening is beyond my expectation. I devoted a lot of time and energy to uncover the functions of those indispensable genes and study the mechanisms underlying those molecules. I will have more publications from the genes I knocked out than expected and more importantly, most of them will be very important for the field of mammalian reproductive biology. Although the CONVID-19 spreading deviates us from focusing on academic research, after the pandemic ceases, I hope I can keep the pace and publish more papers with good quality.
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| Strategy for Future Research Activity |
Other essential male genes that I discovered are currently being studied in terms of their mechanisms in underpinning male reproduction and their potential to serve as targets for non-hormonal male contraceptives. I would expect to publish at least two or three more papers before the end of the funding period.
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