Kiss1-/- mice exhibit more variable hypogonadism than Gpr54-/- mice
Kiss1-/- mice exhibit more variable hypogonadism than Gpr54-/- mice
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DOI：
10.1210/en.2007-0078
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发表时间：
2007-10-01
期刊：
影响因子：
4.8
通讯作者：
Seminara, Stephanie B.
中科院分区：
文献类型：
--
作者：
Lapatto, Risto;Pallais, J. Carl;Seminara, Stephanie B.
G蛋白偶联受体Gpr 54及其配体metastin（来自Kiss 1基因产物kisspeptin）是性成熟的关键守门人。Gpr 54基因敲除小鼠表现出低促性腺激素性性腺功能减退，但直到最近，Kiss 1基因敲除小鼠的表型是未知的。本报告描述了在相同遗传背景下携带Kiss 1或Gpr 54靶向缺失的小鼠的生殖表型。Kiss 1和Gpr 54基因敲除小鼠都能存活，但不育，性成熟异常;大多数雄性缺乏包皮分离，雌性阴道开放延迟，缺乏发情周期。与对照组相比，Kiss 1和Gpr 54基因敲除雄性的睾丸明显较小。gpr 54基因敲除的雌性比野生型雌性具有更小的卵巢和子宫。然而，Kiss 1基因敲除的女性表现出两种不同的表型：一半有显着减少性腺重量类似的Gpr 54基因敲除小鼠，而一半表现出持续的阴道角化和性腺重量与野生型女性。Kiss 1和Gpr 54基因敲除的雄性和雌性的FSH水平均显著低于对照组。当注射小鼠metastin 43-52（一种Gpr 54激动剂）时，Gpr 54敲除小鼠不能增加促性腺激素，而Kiss 1敲除小鼠则以增加促性腺激素水平作出反应。总之，Kiss 1和Gpr 54基因敲除小鼠都具有与低促性腺激素性功能减退症一致的异常性成熟，尽管Kiss 1基因敲除小鼠似乎比其受体对应物受到的影响要轻。Kiss 1基因敲除的雌性动物表现出双峰表型变异，一些动物具有较高的性腺重量，较大的阴道开口，和持续的阴道角化。
The G protein-coupled receptor Gpr54 and its ligand metastin (derived from the Kiss1 gene product kisspeptin) are key gatekeepers of sexual maturation. Gpr54 knockout mice demonstrate hypogonadotropic hypogonadism, but until recently, the phenotype of Kiss1 knockout mice was unknown. This report describes the reproductive phenotypes of mice carrying targeted deletions of Kiss1 or Gpr54 on the same genetic background. Both Kiss1 and Gpr54 knockout mice are viable but infertile and have abnormal sexual maturation; the majority of males lack preputial separation, and females have delayed vaginal opening and absence of estrous cycling. Kiss1 and Gpr54 knockout males have significantly smaller testes compared with controls. Gpr54 knockout females have smaller ovaries and uteri than wild-type females. However, Kiss1 knockout females demonstrate two distinct phenotypes: half have markedly reduced gonadal weights similar to those of Gpr54 knockout mice, whereas half exhibit persistent vaginal cornification and have gonadal weights comparable with those of wild-type females. FSH levels in both Kiss1 and Gpr54 knockout males and females are significantly lower than in controls. When injected with mouse metastin 43-52, a Gpr54 agonist, Gpr54 knockout mice fail to increase gonadotropins, whereas Kiss1 knockout mice respond with increased gonadotropin levels. In summary, both Kiss1 and Gpr54 knockout mice have abnormal sexual maturation consistent with hypogonadotropic hypogonadism, although Kiss1 knockout mice appear to be less severely affected than their receptor counterparts. Kiss1 knockout females demonstrate a bimodal phenotypic variability, with some animals having higher gonadal weight, larger vaginal opening, and persistent vaginal cornification.