Comparative Medicine Department, King Faisal Specialist Hospital and Research Centre, Riyadh, 11211, Saudi Arabia.
Department of Biochemistry and Molecular Biology, Faculty of Veterinary Medicine, Cairo University, Giza, 12613, Egypt.
Sci Rep. 2018 Jun 15;8(1):9202. doi: 10.1038/s41598-018-27379-0.
DDB1- and CUL4-associated factor 17 (Dcaf17) is a member of DCAF family genes that encode substrate receptor proteins for Cullin-RING E3 ubiquitin ligases, which play critical roles in many cellular processes. To unravel the function of DCAF17, we performed expression profiling of Dcaf17 in different tissues of wild type mouse by qRT-PCR and generated Dcaf17 knockout mice by gene targeting. Expression profiling of Dcaf17 showed highest expression in testis. Analyses of Dcaf17 transcripts during post-natal development of testis at different ages displayed gradual increase in Dcaf17 mRNA levels with the age. Although Dcaf17 disruption did not have any effect on female fertility, Dcaf17 deletion led to male infertility due to abnormal sperm development. The Dcaf17 mice produced low number of sperm with abnormal shape and significantly low motility. Histological examination of the Dcaf17 testis revealed impaired spermatogenesis with presence of vacuoles and sloughed cells in the seminiferous tubules. Disruption of Dcaf17 caused asymmetric acrosome capping, impaired nuclear compaction and abnormal round spermatid to elongated spermatid transition. For the first time, these data indicate that DCAF17 is essential for spermiogenesis.
DDB1- 和 CUL4 相关因子 17（Dcaf17）是 DCAF 家族基因的成员，该家族基因编码 Cullin-RING E3 泛素连接酶的底物受体蛋白，在许多细胞过程中发挥着关键作用。为了阐明 DCAF17 的功能，我们通过 qRT-PCR 对野生型小鼠不同组织中的 Dcaf17 进行了表达谱分析，并通过基因靶向生成了 Dcaf17 敲除小鼠。Dcaf17 的表达谱分析显示，其在睾丸中的表达最高。对不同年龄阶段睾丸出生后发育过程中 Dcaf17 转录本的分析显示，Dcaf17 mRNA 水平随年龄逐渐增加。尽管 Dcaf17 缺失对雌性生育能力没有影响，但由于精子发育异常，Dcaf17 缺失导致雄性不育。Dcaf17 小鼠产生的精子数量少，形状异常，运动能力显著降低。Dcaf17 睾丸的组织学检查显示，精子发生受损，生精小管中存在空泡和脱落细胞。Dcaf17 的破坏导致顶体不对称帽形成、核浓缩受损和异常圆形精子向伸长精子的转变。这些数据首次表明 DCAF17 对精子发生是必不可少的。
