Implication of nanos2-3′UTR in the expression and function of nanos2
Implication of nanos2-3′UTR in the expression and function of nanos2
复制标题
DOI：
10.1016/j.mod.2006.04.002
复制
发表时间：
2006-06
影响因子：
2.6
通讯作者：
M. Tsuda;M. Kiso;Y. Saga
中科院分区：
文献类型：
--
作者：
M. Tsuda;M. Kiso;Y. Saga
基因表达的翻译调控是调控细胞分化和发育的重要组成部分。为了阐明nanos2基因的3 '非翻译区（UTR）在小鼠体内的功能，我们比较了lacZ敲入小鼠的表型，发现nanos2基因的这一区域在生殖细胞的翻译调控中具有潜在的作用。nanos2-3'UTR在卵母细胞中抑制mRNA的翻译，但在雄性性腺中促进蛋白质的产生。为了进一步了解nanos2 3'UTR在体内的意义，我们构建了内源性缺乏该区域的小鼠细胞系nanos2pA/pA。在nanos2−/pAmice中，与nanos2pA/pAmice相比，生殖细胞缺失的精管数量增加，表明精子发生存在剂量依赖性缺陷。这些结果表明，nanos2蛋白水平对正常精子发生至关重要，并且该途径可能通过nanos2-3 ' utr进行调节。我们发现nanos2pA/ paa和nanos2 - /pAmice的缺陷是由胚胎性腺和新生儿睾丸中性腺细胞/精原细胞的凋亡引起的。此外，研究指出，出生后，nanos2的表达仅限于特定的精原细胞亚群，这表明nanos2在新生儿睾丸中卵泡细胞/精原细胞的维持和分化中起作用。
Translational control of gene expression is an important component of the regulation of cellular differentiation and development. To elucidate the function of the 3′untranslated region (UTR) of the nanos2 gene in mice, we compared the phenotypes of lacZ knock-in mice with or without a native nanos2 3′UTR and found that this region of the nanos2 gene has a potential role during translational regulation in germ cells. The nanos2-3′UTR functions to repress the translation of mRNA in oocytes, but enhances the production of protein in the male gonads. To further understand the significance of the nanos2 3′UTR in vivo, we generated the mouse line nanos2pA/pA, which lacks this region endogenously. In nanos2−/pAmice, the number of germ cell-depleted seminiferous tubules was increased when compared with that of nanos2pA/pAmice, indicating a dose-dependent defect in spermatogenesis. These results suggest that the level of nanos2 protein is critical for normal spermatogenesis, and that this pathway may be regulated through the nanos2-3′UTR. We found that the defects in nanos2pA/pAand nanos2−/pAmice were caused by apoptosis of gonocytes in the embryonic gonads and gonocyte/spermatogonia in neonatal testes. In addition, it was noted that the nanos2 expression was restricted to a particular subset of spermatogonia after birth, which indicates that nanos2 plays a role in the maintenance and differentiation of gonocytes/spermatogonia in neonatal testes.