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生殖细胞中β-连环蛋白基因缺失的雄性小鼠的正常生育能力。

Normal fertility in male mice with deletion of β-catenin gene in germ cells.

作者信息

Rivas Bryan, Huang Zaohua, Agoulnik Alexander I

机构信息

Department of Human and Molecular Genetics, Herbert Wertheim College of Medicine, Florida International University, Miami, Florida.

出版信息

Genesis. 2014 Apr;52(4):328-32. doi: 10.1002/dvg.22742. Epub 2014 Jan 31.

Abstract

As a dual function protein, β-catenin affects both cell adhesion and mediates canonical Wnt/β-catenin cell signaling. β-Catenin is prominently expressed in somatic Sertoli cells in the testis and postmeiotic germ cells, suggesting an additional role in spermatogenesis. It was reported previously that Cre/loxP-mediated conditional inactivation of the β-catenin gene (Ctnnb1) in male gonads using a protamine promoter-driven Cre transgene (Prm-cre) resulted in partial infertility, reduced sperm count, and abnormal spermatogenesis. In this report, we demonstrated that the conditional deletion of Ctnnb1 using a germ cell specific Cre transgene (Stra8-icre) had no effect on male fertility. We have shown that the Stra8-icre transgene was highly efficient in generating deletion in early pre-meiotic and post-meiotic cells. No differences in anatomical or histological presentation were found in the mutant testis, the production of viable sperm was similar, and no abnormalities in DNA sperm content were detected. We concluded that β-catenin is fully dispensable in germ cells for spermatogenesis. The conflicting results from the earlier study may have been due to off-target expression of Prm-cre in testicular somatic cells. In future studies, the analysis of conditional mutants using several Cre-transgenes should be encouraged to reduce potential errors.

摘要

作为一种具有双重功能的蛋白质,β-连环蛋白既影响细胞黏附,又介导经典的Wnt/β-连环蛋白细胞信号传导。β-连环蛋白在睾丸中的体细胞支持细胞和减数分裂后的生殖细胞中显著表达,这表明它在精子发生过程中可能还有其他作用。此前有报道称,使用鱼精蛋白启动子驱动的Cre转基因(Prm-cre),通过Cre/loxP介导在雄性性腺中条件性失活β-连环蛋白基因(Ctnnb1),会导致部分不育、精子数量减少和精子发生异常。在本报告中,我们证明使用生殖细胞特异性Cre转基因(Stra8-icre)条件性缺失Ctnnb1对雄性生育力没有影响。我们已经表明,Stra8-icre转基因在早期减数分裂前和减数分裂后细胞中产生缺失的效率很高。在突变睾丸中未发现解剖学或组织学表现的差异,活精子的产生相似,并且未检测到精子DNA含量异常。我们得出结论,β-连环蛋白在生殖细胞的精子发生过程中是完全可有可无的。早期研究中相互矛盾的结果可能是由于Prm-cre在睾丸体细胞中的脱靶表达所致。在未来的研究中,应鼓励使用多种Cre转基因对条件性突变体进行分析,以减少潜在误差。

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