Targeted disruption of the Insl3 gene causes bilateral cryptorchidism.
Targeted disruption of the Insl3 gene causes bilateral cryptorchidism.
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DOI：
10.1210/mend.13.5.0272
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发表时间：
1999-05
影响因子：
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通讯作者：
S. Zimmermann;G. Steding;J. Emmen;A. Brinkmann;K. Nayernia;A. Holstein;W. Engel;I. Adham
中科院分区：
文献类型：
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作者：
S. Zimmermann;G. Steding;J. Emmen;A. Brinkmann;K. Nayernia;A. Holstein;W. Engel;I. Adham
哺乳动物性腺的性二态性位置取决于两个韧带的差异发育，即颅悬韧带（CSL）和结节。在男性胚胎发生过程中，结节的生长和CSL的退化导致睾丸经腹下降，而在女性中，CSL的发育与结节发育的失败相结合，使卵巢保持在肾脏侧面的位置。多项证据表明，CSL 的消退和结节发育的诱导分别是由睾酮和尚未确定的睾丸因子介导的。 Insl3 基因（最初命名为 Ley I-L）是胰岛素样超家族的成员，在胎儿和出生后睾丸的 Leydig 细胞以及出生后卵巢的卵泡膜细胞中特异性表达。在这里，我们发现 Insl3 基因座定向删除的纯合雄性小鼠表现出双侧隐睾，具有自由移动的睾丸和生殖管。这些畸形是由于胚胎发生过程中结节发育失败造成的。在 Insl3 和雄激素受体基因双突变雄性小鼠中，睾丸位于肾脏附近，并通过 CSL 稳定在腹部。这些发现表明，Insl3 以不依赖于雄激素的方式诱导生殖器发育，而雄激素介导的 CSL 消退独立于 Insl3 发生。
The sexual dimorphic position of the gonads in mammals is dependent on differential development of two ligaments, the cranial suspensory ligament (CSL) and the gubernaculum. During male embryogenesis, outgrowth of the gubernaculum and regression of the CSL result in transabdominal descent of the testes, whereas in the female, development of the CSL in conjunction with failure of the gubernaculum development holds the ovaries in a position lateral to the kidneys. Several lines of evidence suggest that regression of the CSL and induction of gubernaculum development are mediated by testosterone and a yet unidentified testicular factor, respectively. The Insl3 gene (originally designated Ley I-L), a member of the insulin-like superfamily, is specifically expressed in Leydig cells of the fetal and postnatal testis and in theca cells of the postnatal ovary. Here we show that male mice homozygous for a targeted deletion of the Insl3 locus exhibit bilateral cryptorchidism with free moving testes and genital ducts. These malformations are due to failure of gubernaculum development during embryogenesis. In double-mutant male mice for Insl3 and androgen receptor genes, testes are positioned adjacent to the kidneys and steadied in the abdomen by the CSL. These findings demonstrate, that the Insl3 induces gubernaculum development in an androgen-independent way, while androgen-mediated regression of the CSL occurs independently from Insl3.