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首页> 外文期刊>Molecular and Cellular Biology >Infertility with Defective Spermiogenesis in Mice Lacking AF5q31, the Target of Chromosomal Translocation in Human Infant Leukemia
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Infertility with Defective Spermiogenesis in Mice Lacking AF5q31, the Target of Chromosomal Translocation in Human Infant Leukemia

机译：缺乏AF5q31，人类婴儿白血病的染色体易位的目标的小鼠有缺陷的精子发生不育。

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AF5q31 (also called MCEF) was identified by its involvement in chromosomal translocation with the gene MLL (mixed lineage leukemia), which is associated with infant acute lymphoblastic leukemia. Several potential roles have been proposed for AF5q31 and other family genes, but the specific requirements of AF5q31 during development remain unclear. Here, we show that AF5q31 is essential for spermatogenesis. Although most AF5q31-deficient mice died in utero and neonatally with impaired embryonic development and shrunken alveoli, respectively, 13% of AF5q31-deficient mice thrived as wild-type mice did. However, the male mice were sterile with azoospermia. Histological examinations revealed the arrest of germ cell development at the stage of spermiogenesis, and virtually no spermatozoa were seen in the epididymis. AF5q31 was found to be preferentially expressed in Sertoli cells. Furthermore, mutant mice displayed severely impaired expression of protamine 1, protamine 2, and transition protein 2, which are indispensable to compact the haploid genome within the sperm head, and an increase of apoptotic cells in seminiferous tubules. Thus, AF5q31 seems to function as a transcriptional regulator in testicular somatic cells and is essential for male germ cell differentiation and survival. These results may have clinical implications in the understanding of human male infertility.
机译：通过与婴儿相关的基因 MLL （混合谱系白血病）参与了染色体易位，鉴定出 AF5q31 （也称为 MCEF ）急性淋巴细胞白血病。已经提出了AF5q31和其他家族基因的几种潜在作用，但是AF5q31在发育过程中的具体要求仍不清楚。在这里，我们显示AF5q31对于精子发生必不可少。尽管大多数AF5q31缺乏症小鼠分别在子宫和新生儿中死亡，胚胎发育受损，肺泡萎缩，但仍有13％的AF5q31缺乏症小鼠像野生型小鼠一样蓬勃发展。然而，雄性小鼠无精子症是不育的。组织学检查显示，在精子发生阶段停止了生殖细胞的发育，实际上在附睾中未见到精子。发现AF5q31在Sertoli细胞中优先表达。此外，突变小鼠显示出精蛋白1，精蛋白2和过渡蛋白2的表达严重受损，这对于压缩精子头内的单倍体基因组是必不可少的，而生精小管中的凋亡细胞则增加。因此，AF5q31似乎在睾丸体细胞中起转录调节剂的作用，对于雄性生殖细胞的分化和存活至关重要。这些结果可能对理解男性不育症具有临床意义。

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