TALEN-Mediated Gene Disruption on Y Chromosome Reveals Critical Role of EIF2S3Y in Mouse Spermatogenesis
TALEN-Mediated Gene Disruption on Y Chromosome Reveals Critical Role of EIF2S3Y in Mouse Spermatogenesis
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DOI：
10.1089/scd.2014.0466
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发表时间：
2015-05-15
影响因子：
4
通讯作者：
Asahara, Hiroshi
中科院分区：
文献类型：
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作者：
Matsubara, Yohei;Kato, Tomoko;Asahara, Hiroshi
Y染色体在精子发生中起着至关重要的作用。以前，使用传统的基因靶向策略很难培育出具有特定 Y 染色体突变的基因敲除小鼠。最近，一种转录激活因子样效应核酸酶（TALEN）被成功用于编辑小鼠 Y 染色体连锁基因。在这里，我们报告了带有 Y 染色体连锁基因 Eif2s3y 突变的小鼠模型的生成，并分析了其表型。携带 Eif2s3y 靶向突变的小鼠不育且睾丸发育不全。组织学和电子显微镜分析表明，精原细胞的分化在精原干细胞（未分化精原细胞）阶段被阻止，精子发生的进程被中断，导致无精子症。使用 TALEN，我们验证了 EIF2S3Y 在精原干细胞分化中发挥关键功能。
The Y chromosome plays a critical role in spermatogenesis. Formerly, it had been difficult to generate knockout mice with specific Y chromosome mutations using conventional gene-targeting strategies. Recently, a transcription activator-like effector nuclease (TALEN) was successfully used for editing a mouse Y chromosome-linked gene. Here, we report the generation of a mouse model with a mutation in Eif2s3y, a Y chromosome-linked gene, and analysis of its phenotype. The mouse carrying a targeted mutation of Eif2s3y was infertile and had hypoplastic testes. Histological and electron microscopic analyses showed that differentiation of spermatogonia was arrested at the stage of spermatogonial stem cells (undifferentiated spermatogonia) and that the progression of spermatogenesis was interrupted, resulting in azoospermia. Using TALEN, we verified that EIF2S3Y performs a key function in differentiation of spermatogonial stem cells.