Print C G, Loveland K L, Gibson L, Meehan T, Stylianou A, Wreford N, de Kretser D, Metcalf D, Köntgen F, Adams J M, Cory S
The Walter and Eliza Hall Institute of Medical Research, Post Office, Royal Melbourne Hospital, Victoria 3050, Australia.
Proc Natl Acad Sci U S A. 1998 Oct 13;95(21):12424-31. doi: 10.1073/pnas.95.21.12424.
Proteins of the Bcl-2 family are important regulators of apoptosis in many tissues of the embryo and adult. The recently isolated bcl-w gene encodes a pro-survival member of the Bcl-2 family, which is widely expressed. To explore its physiological role, we have inactivated the bcl-w gene in the mouse by homologous recombination. Mice that lack Bcl-w were viable, healthy, and normal in appearance. Most tissues exhibited typical histology, and hematopoiesis was unaffected, presumably due to redundant function with other pro-survival family members. Although female reproductive function was normal, the males were infertile. The testes developed normally, and the initial, prepubertal wave of spermatogenesis was largely unaffected. The seminiferous tubules of adult males, however, were disorganized, contained numerous apoptotic cells, and produced no mature sperm. Both Sertoli cells and germ cells of all types were reduced in number, the most mature germ cells being the most severely depleted. The bcl-w-/- mouse provides a unique model of failed spermatogenesis in the adult that may be relevant to some cases of human male sterility.
Bcl-2家族蛋白是胚胎和成年动物许多组织中细胞凋亡的重要调节因子。最近分离出的bcl-w基因编码Bcl-2家族的一个促生存成员，该成员广泛表达。为了探究其生理作用，我们通过同源重组使小鼠中的bcl-w基因失活。缺乏Bcl-w的小鼠存活、健康且外观正常。大多数组织呈现典型的组织学特征，造血功能未受影响，这可能是由于与其他促生存家族成员功能冗余。虽然雌性生殖功能正常，但雄性不育。睾丸发育正常，青春期前的初始精子发生波基本未受影响。然而，成年雄性的生精小管结构紊乱，含有大量凋亡细胞，且不产生成熟精子。支持细胞和所有类型的生殖细胞数量均减少，最成熟的生殖细胞减少最为严重。bcl-w-/-小鼠为成年动物精子发生失败提供了一个独特的模型，这可能与人类男性不育的某些病例相关。
