Spermatogonial deubiquitinase USP9X is essential for proper spermatogenesis in mice
Spermatogonial deubiquitinase USP9X is essential for proper spermatogenesis in mice
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DOI：
10.1530/rep-17-0184
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发表时间：
2017-08-01
期刊：
影响因子：
3.8
通讯作者：
Kanai, Yoshiakira
中科院分区：
文献类型：
--
作者：
Kishi, Kasane;Uchida, Aya;Kanai, Yoshiakira
USP9X（泛素特异性肽酶9，X染色体）是哺乳动物果蝇去泛素酶脂肪方面的同源基因，先前已被证明通过稳定Vasa来部分调节生殖细胞谱系的维持，Vasa是配子体发生中广泛保守的关键因子之一。在这里，我们证明了USP9X在从新生儿到成年阶段的小鼠睾丸的性腺细胞和精原细胞中表达。通过使用Vasa-Cre小鼠，从胚胎期开始的生殖细胞特异性条件缺失Usp9x在1周内未在发育中的睾丸中出现异常，并且在出生后和成年期未分化和分化的精原细胞中没有明显的缺陷。有趣的是，2周后，Usp9x缺失的生精细胞在早期精母细胞阶段发生凋亡细胞死亡，随后导致精子发生异常，导致Usp9x条件敲除雄鼠完全不育。这些数据首次证明了精原基因USP9X在USP9X条件敲除睾丸从有丝分裂阶段过渡到减数分裂阶段和/或维持减数分裂早期阶段的关键作用。
USP9X (ubiquitin-specific peptidase 9, X chromosome) is the mammalian orthologue of Drosophila deubiquitinase fat facets that was previously shown to regulate the maintenance of the germ cell lineage partially through stabilizing Vasa, one of the widely conserved factors crucial for gametogenesis. Here, we demonstrate that USP9X is expressed in the gonocytes and spermatogonia in mouse testes from newborn to adult stages. By using Vasa-Cre mice, germ cell-specific conditional deletion of Usp9x from the embryonic stage showed no abnormality in the developing testes by 1 week and no appreciable defects in the undifferentiated and differentiating spermatogonia at postnatal and adult stages. Interestingly, after 2 weeks, Usp9x-null spermatogenic cells underwent apoptotic cell death at the early spermatocyte stage, and then, caused subsequent aberrant spermiogenesis, which resulted in a complete infertility of Usp9x conditional knockout male mice. These data provide the first evidence of the crucial role of the spermatogonial USP9X during transition from the mitotic to meiotic phases and/or maintenance of early meiotic phase in Usp9x conditional knockout testes.