A novel requirement in mammalian spermatid differentiation for the DAZ-family protein Boule.
A novel requirement in mammalian spermatid differentiation for the DAZ-family protein Boule.
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DOI：
10.1093/hmg/ddq109
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发表时间：
2010-06
影响因子：
3.5
通讯作者：
Michael J W Vangompel;E. Xu
中科院分区：
文献类型：
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作者：
Michael J W Vangompel;E. Xu
繁殖是所有动物生存所必需的，然而很少有生殖基因被证明对整个动物王国的生育能力有保守的要求。值得注意的是，RNA结合蛋白BOULE是DAZ（在无精子症中缺失）基因家族中最古老的成员，似乎从昆虫到人类都保持了其保守的功能基序和生精表达。在雄性果蝇和雌性秀丽隐杆线虫中，Boule突变导致粗线减数分裂在中期前停止，而人类Boule可以恢复果蝇睾丸的减数分裂，表明人类Boule具有保守的减数分裂功能。然而，BOULE在哺乳动物中的生理功能尚不清楚。我们培育了Boule基因敲除小鼠，发现它只在精子发生时才需要，就像果蝇一样。有趣的是，在没有Boule的情况下，减数分裂正常完成，单倍体圆形精子很容易被检测到。然而，圆形精子没有超过第6步，这揭示了Boule在精子发生中的新作用，即圆形精子向成熟精子的分化。在Boule（-/-）小鼠中，精子发生的关键调控因子的表达不受影响，这表明Boule通过一种新的途径调节生殖细胞分化。
Reproduction is required for the survival of all animals, yet few reproductive genes have been shown to have a conserved requirement for fertility across the animal kingdom. Remarkably, the RNA binding protein BOULE, the oldest member of the DAZ (Deleted in AZoospermia) family of genes, appears to have maintained its conserved functional motif and spermatogenic expression from insects to humans. Boule mutations lead to a pachytene meiotic arrest before metaphase in Drosophila males and C. elegans females, and human BOULE can restore meiosis in the fly testis, suggesting a conserved meiotic function of human BOULE. However, the physiological function of BOULE in mammals is not yet known. We generated Boule knockout mice and found it to be required only for spermatogenesis, as in Drosophila. Interestingly, meiosis completed normally in the absence of Boule, and haploid round spermatids were readily detected. However, round spermatids did not progress beyond step 6, revealing a novel role for Boule in spermiogenesis, the differentiation of round spermatids into mature spermatozoa. Expression of key regulators of spermiogenesis was unaffected in Boule(-/-) mice, suggesting that Boule regulates germ-cell differentiation through a novel pathway.