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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >A human DAZ transgene confers partial rescue of the mouse Dazl null phenotype
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A human DAZ transgene confers partial rescue of the mouse Dazl null phenotype

机译：人类DAZ转基因可部分拯救小鼠Dazl无效表型

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摘要

In a subset of infertile men, a spectrum of spermatogenic defects ranging from a complete absence of germ cells (sertoli cell only) to oligozoospermia is associated with microdelections of the DAZ (delected in azoospermia) gene cluster on human distal Yq. DAZ encodes a testis-specific protein with RNA-binding potential recently derived from a single-copy gene DAZLI (DAZ-like) on chromosome 3.Y chromosomal DAZ homologues are confined to humans and higher primates. It remains unclear which function unique to higher primate spermatogenesis DAZ may serve, and the functional status of the gene recently has been questioned. To assess the extent of functional conservation we have tested the capacity of a human DAZ gene contained in a 225-kb yeast artificial chromosome to complement the sterile phenotype of the Dazl null mouse (Dazl-1-), which is characterized by severe germ-cell depletion and meiotic failure. Although DAZl-1-mice remained infertile when the DAZ transgene was introduced, histological examination revealed a partial and variable rescue of the mutant phenotype, manifest as a pronounced increase in the germ cell population of the seminiferous tubules and survival to the pachytene stage of meiosis. As well as constituting definitive proof of the spermatogenic role of the DAZ gene product, these findings confirm the high degree of functional conservation between the DAZ and DAZLI genes suggesting they may constitute a single target for contraceptive intervention and raising the possibility of therapeutic up-regulation of the DAZLI gene in infertile men.
机译：在一部分不育男性中，从完全没有生殖细胞（仅睾丸脂细胞）到少精子症的一系列生精缺陷与人远端Yq上DAZ（在无精子症中形成）基因簇的微变形有关。 DAZ编码一种具有RNA结合潜能的睾丸特异性蛋白质，该蛋白质最近来自3号染色体上的单拷贝基因DAZLI（类DAZ）。Y染色体DAZ同源物仅限于人类和高等灵长类动物。尚不清楚哪种功能可以发挥更高的灵长类动物精子生成DAZ的功能，最近对该基因的功能状态提出了质疑。为了评估功能保守性的程度，我们测试了225 KB酵母人工染色体中包含的人类DAZ基因与Dazl空小鼠（Dazl-1-）的无菌表型互补的能力，该表型的特征是严重的细菌-细胞耗竭和减数分裂衰竭。尽管当导入DAZ转基因时DAZ1-1小鼠仍然不育，但是组织学检查显示突变表型的部分和可变拯救，表现为生精小管的生殖细胞群显着增加以及减数分裂的上皮期生存。这些发现不仅构成了DAZ基因产物生精作用的明确证据，还证实了DAZ和DAZLI基因之间高度的功能保守性，表明它们可能构成避孕干预的单一目标，并增加了治疗上调的可能性不育男性中DAZLI基因的表达

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