COP9组成型光形态发生同系物亚基5(COPS5),也被称为Jab1或CSN5,已经涉及到各种各样的细胞和发育过程。通过分析雄性生殖细胞特异性COPS5缺陷小鼠,我们之前证明了COPS5对于维持雄性细菌存活和顶体生物发生至关重要.为了进一步确定Cops5在肾小管周肌样(PTM)细胞中的作用,围绕生精小管的平滑肌谱系,我们在本文中使用转基因Myh11-Cre小鼠衍生出平滑肌细胞(SMC)中的Cops5基因有条件缺陷的小鼠。尽管这些有条件的Cops5缺陷小鼠以预期的孟德尔比率出生,并且在出生后的第一周内似乎是正常的,纯合小鼠在一周后开始表现出生长迟缓。这些小鼠还表现出各种发育和生殖障碍,包括男性和女性生殖器官发育的失败,精子发生缺陷,骨骼发育受损,和免疫功能。此外,条件性Cops5缺陷小鼠揭示了与睾丸功能相关的内分泌系统的严重损害,包括血清促性腺激素水平显著降低(FSH,LH),睾丸激素,胰岛素样生长因子1(IGF1),和葡萄糖,但不是加压素.在研究中,所有纯合小鼠在67日龄之前死亡。总的来说,我们的研究结果提供了新的证据,表明平滑肌谱系中的Cops5在出生后发育和生殖功能中起着至关重要的作用。
COP9 constitutive photomorphogenic homolog subunit 5 (
COPS5), also known as Jab1 or CSN5, has been implicated in a wide variety of cellular and developmental processes. By analyzing male germ cell-specific
COPS5-deficient mice, we have demonstrated previously that
COPS5 is essential to maintain male germ survival and acrosome biogenesis. To further determine the role of
Cops5 in peritubular myoid cells, a smooth muscle lineage surrounding seminiferous tubules, we herein derived mice conditionally deficient for the
Cops5 gene in smooth muscle cells using transgenic Myh11-Cre mice. Although these conditional
Cops5-deficient mice were born at the expected Mendelian ratio and appeared to be normal within the first week after birth, the homozygous mice started to show growth retardation after 1 week. These mice also exhibited a variety of developmental and reproductive disorders, including failure of development of reproductive organs in both males and females, spermatogenesis defects, and impaired skeletal development and immune functions. Furthermore, conditional Cops5-deficient mice revealed dramatic impairment of the endocrine system associated with testicular functions, including a marked reduction in serum levels of gonadotropins (follicle-stimulating hormone, luteinizing hormone), testosterone, insulin-like growth factor 1, and glucose, but not vasopressin. All homozygous mice died before age 67 days in the study. Collectively, our results provide novel evidence that Cops5 in smooth muscle lineage plays an essential role in postnatal development and reproductive functions.