Ehd4 is Required to Attain Normal Prepubertal Testis Size but Dispensable for Fertility in Male Mice
Ehd4 is Required to Attain Normal Prepubertal Testis Size but Dispensable for Fertility in Male Mice
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DOI：
10.1002/dvg.20620
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发表时间：
2010-05-01
期刊：
影响因子：
1.5
通讯作者：
Band, Hamid
中科院分区：
文献类型：
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作者：
George, Manju;Rainey, Mark A.;Band, Hamid
C 端 EH 结构域 (EHD) 蛋白家族 (EHD1-4) 的四个高度同源的成员调节内吞再循环。为了描述 EHD4 在正常生理和发育中的作用，产生了 Ehd4 基因条件性敲除的小鼠。基因组 DNA 的 PCR 和 Ehd4(-/-) 小鼠器官裂解物的蛋白质印迹证实了 EHD4 缺失。 Ehd4(-/-) 小鼠能够存活并以预期的孟德尔比率出生；然而，雄性的睾丸重量减少了 50%，从出生后第 31 天开始就很明显。在 Ehd4(-/-) 睾丸中，生殖细胞增殖和凋亡早期（第 10 天）增加，细胞凋亡后期（第 31 天）增加。其他缺陷包括生精小管直径逐渐减小、生精上皮失调以及细长精子细胞的头部异常。结果，在 Ehd4(-/-) 男性中观察到精子数量减少和生育能力下降。有趣的是，EHD 蛋白表达在睾丸中受到暂时调节，EHD4 水平在第 10 天至 15 天之间达到峰值。在成人睾丸中，EHD4 在初级精母细胞中高度表达，EHD4 缺失以年龄依赖性方式改变了其他 EHD 蛋白的水平。我们得出的结论是，成人 Ehd4(-/-) 睾丸中高水平的 EHD1 可以在功能上补偿 EHD4 的缺乏，并防止严重生育缺陷的发展。我们的结果表明 EHD4 在有丝分裂后和减数分裂后生殖细胞的正常发育中发挥作用，并表明 EHD 蛋白介导的内吞再循环是生殖细胞发育和睾丸功能的重要过程。创世纪 48:328-342, 2010。(C) 2010 Wiley-Liss, Inc.
The four highly homologous members of the C-terminal EH domain-containing (EHD) protein family (EHD1-4) regulate endocytic recycling. To delineate the role of EHD4 in normal physiology and development, mice with a conditional knockout of the Ehd4 gene were generated. PCR of genomic DNA and Western blotting of organ lysates from Ehd4(-/-) mice confirmed EHD4 deletion. Ehd4(-/-) mice were viable and born at expected Mendelian ratios; however, males showed a 50% reduction in testis weight, obvious from postnatal day 31. An early (Day 10) increase in germ cell proliferation and apoptosis and a later increase in apoptosis (Day 31) were seen in the Ehd4(-/-) testis. Other defects included a progressive reduction in seminiferous tubule diameter, dysregulation of seminiferous epithelium, and head abnormalities in elongated spermatids. As a consequence, lower sperm counts and reduced fertility were observed in Ehd4(-/-) males. Interestingly, EHD protein expression was seen to be temporally regulated in the testis and EHD4 levels peaked between days 10 and 15. In the adult testis, EHD4 was highly expressed in primary spermatocytes and EHD4 deletion altered the levels of other EHD proteins in an age-dependent manner. We conclude that high levels of EHD1 in the adult Ehd4(-/-) testis functionally compensate for lack of EHD4 and prevents the development of severe fertility defects. Our results suggest a role for EHD4 in the proper development of postmitotic and postmeiotic germ cells and implicate EHD protein-mediated endocytic recycling as an important process in germ cell development and testis function. genesis 48:328-342, 2010. (C) 2010 Wiley-Liss, Inc.