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/me.13.5.681
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发表时间：
1999-05-01
影响因子：
--
通讯作者：
Adham, IM
中科院分区：
文献类型：
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作者：
Zimmermann, S;Steding, G;Adham, IM
哺乳动物性腺的两性位置取决于颅悬韧带（CSL）和引带（gubernaculum）的发育差异。在雄性胚胎发生过程中，引带的生长和CSL的退化导致睾丸的经腹下降，而在雌性中，CSL的发育与引带发育的失败一起将卵巢保持在肾脏的侧面位置。有证据表明CSL的退化和引带发育的诱导分别由睾酮和一种尚未鉴定的睾丸因子介导。Ins/3基因（最初命名为Ley I-L）是胰岛素样超家族的成员，特异性地表达于胎儿和出生后睾丸的Leydig细胞和出生后卵巢的卵泡膜细胞中。在这里，我们表明，雄性小鼠纯合子的lns/3基因座的目标删除表现出双侧隐睾症与自由移动的睾丸和生殖导管。这些畸形是由于胚胎发生过程中引带发育失败所致。在Ins/3和雄激素受体基因的双突变雄性小鼠中，睾丸位于肾脏附近并被CSL包裹在腹部。这些发现表明，Ins/3以雄激素非依赖性方式诱导引带发育，而雄激素介导的CSL退化独立于Ins/3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 Ins/3 gene (orginally 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 lns/3 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 Ins/3 and androgen receptor genes, testes are positioned adjacent to the kidneys and steadied in the abdomen by the CSL, These findings demonstrate, that the lns/3 induces gubernaculum development in an androgen-independent way, while androgen-mediated regression of the CSL occurs independently from lns/3.