The gene encoding bone morphogenetic protein 8B is required for the initiation and maintenance of spermatogenesis in the mouse.
The gene encoding bone morphogenetic protein 8B is required for the initiation and maintenance of spermatogenesis in the mouse.
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DOI：
10.1101/gad.10.13.1657
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发表时间：
1996-07
影响因子：
10.5
通讯作者：
Guang-Quan Zhao;Ke-Yu Deng;P. Labosky;Lucy Liaw;Brigid L. M. Hogan
中科院分区：
文献类型：
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作者：
Guang-Quan Zhao;Ke-Yu Deng;P. Labosky;Lucy Liaw;Brigid L. M. Hogan
骨形态发生蛋白8B（BMP8B）是生长因子的TGF β超家族的成员。在小鼠中，Bmp8b在睾丸的雄性生殖细胞和胎盘的滋养层细胞中表达，表明它在精子发生和生殖中起作用。为了研究这些可能性，我们已经产生了在Bmp8b中具有靶向突变的小鼠。在这里，我们表明，纯合子Bmp8b（tm1blh）突变男性表现出不同程度的生殖细胞缺陷和不育。详细的分析揭示了纯合突变睾丸中两个可分离的缺陷。首先，在青春期早期（2周龄或更小），所有纯合突变体的生殖细胞要么不能增殖，要么增殖显着减少，分化延迟。其次，在成年人中，精母细胞的程序性细胞死亡（凋亡）显著增加，导致生殖细胞耗竭和不育。支持细胞和间质细胞在突变体中相对不受影响。因此，这项研究提供了第一个遗传学证据表明，小鼠生殖细胞产生的因子，BMP 8B，需要恢复男性生殖细胞增殖在青春期早期，生殖细胞存活和生育能力的成年。
Bone morphogenetic protein 8B (BMP8B) is a member of the TGFbeta superfamily of growth factors. In the mouse, Bmp8b is expressed in male germ cells of the testis and trophoblast cells of the placenta, suggesting that it has a role in spermatogenesis and reproduction. To investigate these possibilities, we have generated mice with a targeted mutation in Bmp8b. Here, we show that homozygous Bmp8b(tm1blh) mutant males exhibit variable degrees of germ-cell deficiency and infertility. Detailed analysis reveals two separable defects in the homozygous mutant testes. First, during early puberty (2 weeks old or younger) the germ cells of all homozygous mutants either fail to proliferate or show a marked reduction in proliferation and a delayed differentiation. Second, in adults, there is a significant increase in programmed cell death (apoptosis) of spermatocytes, leading to germ-cell depletion and sterility. Sertoli cells and Leydig cells appear relatively unaffected in mutants. This study therefore provides the first genetic evidence that a murine germ cell-produced factor, BMP8B, is required for the resumption of male germ-cell proliferation in early puberty, and for germ-cell survival and fertility in the adult.