Rad18 is required for long-term maintenance of spermatogenesis in mouse testes
Rad18 is required for long-term maintenance of spermatogenesis in mouse testes
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DOI：
10.1016/j.mod.2008.11.004
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发表时间：
2009-03-01
影响因子：
2.6
通讯作者：
Tateishi, Satoshi
中科院分区：
文献类型：
--
作者：
Sun, Jinghua;Yomogida, Kentaro;Tateishi, Satoshi
维持生精干细胞的完整性对于将遗传信息传递给后代至关重要。然而，关于干细胞遗传稳定性维持的知识仍然有限。RAD18通过增殖细胞核抗原（PCNA）的单泛素化和多泛素化对复制后修复至关重要，以维持基因组的稳定性。哺乳动物RAD18在成年小鼠精母细胞和少数精原细胞核中高度表达。为了阐明RAD18的生理功能，我们分析了RAD18 -/-小鼠的表型。这些老鼠出生了，看起来生长正常。虽然小鼠具有生殖力，但生殖力和睾丸重量随着年龄的增长而下降。2月龄Rad18-/-睾丸的组织学检查显示，几乎所有精管精子发生正常，附睾未见异常精子。然而，25%的小管在12个月时几乎失去了所有的生殖细胞。精小管中经常只保留晚期分化期的生殖细胞，提示精原干细胞的衰竭导致精小管中所有生殖细胞的丢失。野生型生殖细胞成功移植到老年Rad18-/-小鼠的精管中并定植，表明即使在老年睾丸中，Sertoli细胞也具有正常的支持功能。我们得出结论，RAD18是长期维持精子发生所必需的。2008爱思唯尔爱尔兰有限公司版权所有。
Maintaining the integrity of spermatogenic stem cells is essential to transfer genetic information to a descendant. However, knowledge of maintenance of genetic stability in stem cells is still limited. RAD18 is critical for postreplication repair through mono- and multiubiquitination of proliferating cell nuclear antigen (PCNA) to maintain genomic stability. Mammalian RAD18 is highly expressed in the spermatocytes and the nuclei of a few spermatogonia in adult mice. To elucidate the physiological function of RAD18, we analyzed a phenotype of Rad18-/- mice. The mice were born and appeared to grow normally. Although the mice were fertile, fertility and testis weight decreased with age. Histological examination revealed normal spermatogenesis in almost all seminiferous tubules in Rad18-/- testes at 2 months old, and abnormal sperm could not be detected in the epididymis. However, 25% of the tubules lost almost all germ cells at 12 months. The seminiferous tubules frequently retained only late differentiated phase germ cells, suggesting that the exhaustion of spermatogonial stem cells leads to the loss of all germ cells in the seminiferous tubules. Wild-type germ cells were successfully transplanted into and colonized in the seminiferous tubules of aged Rad18-/- mice, indicating that Sertoli cells have a normal supportive function even in aged testes. We conclude that RAD18 is intrinsically required for the long-term maintenance of spermatogenesis. (C) 2008 Elsevier Ireland Ltd. All rights reserved.