2023-04-17 ワシントン州立大学(WSU)
この遺伝子は、様々な哺乳類種にわたって見出されたため、非ホルモン男性避妊薬として有望だと考えられている。今後、この遺伝子を標的とする薬剤の開発に向けた研究が行われる予定である。遺伝子が哺乳類種全体にわたって存在しているため、家畜や野生動物における繁殖管理に応用できる可能性があるという。
<関連情報>
- https://news.wsu.edu/press-release/2023/04/17/new-genetic-target-for-male-contraception-identified/
- https://www.nature.com/articles/s41467-023-37735-y
ARRDC5の発現は哺乳類の精巣で保存されており、正常な精子の形態形成に必要。 ARRDC5 expression is conserved in mammalian testes and required for normal sperm morphogenesis
Mariana I. Giassetti,Deqiang Miao,Nathan C. Law,Melissa J. Oatley,Julie Park,LeeLa D. Robinson,Lisette A. Maddison,Miranda L. Bernhardt & Jon M. Oatley
Nature Communications Published:17 April 2023
DOI:https://doi.org/10.1038/s41467-023-37735-y
Abstract
In sexual reproduction, sperm contribute half the genomic material required for creation of offspring yet core molecular mechanisms essential for their formation are undefined. Here, the α-arrestin molecule arrestin-domain containing 5 (ARRDC5) is identified as an essential regulator of mammalian spermatogenesis. Multispecies testicular tissue transcriptome profiling indicates that expression of Arrdc5 is testis enriched, if not specific, in mice, pigs, cattle, and humans. Knockout of Arrdc5 in mice leads to male specific sterility due to production of low numbers of sperm that are immotile and malformed. Spermiogenesis, the final phase of spermatogenesis when round spermatids transform to spermatozoa, is defective in testes of Arrdc5 deficient mice. Also, epididymal sperm in Arrdc5 knockouts are unable to capacitate and fertilize oocytes. These findings establish ARRDC5 as an essential regulator of mammalian spermatogenesis. Considering the role of arrestin molecules as modulators of cellular signaling and ubiquitination, ARRDC5 is a potential male contraceptive target.
