Department of Applied Life Sciences, Faculty of Agriculture, Shizuoka University, Shizuoka, Japan.
Department of Agriculture, Graduate School of Integrated Science and Technology, Shizuoka University, Shizuoka, Japan.
Sci Rep. 2020 Nov 3;10(1):18883. doi: 10.1038/s41598-020-75957-y.
Deleted in lung and esophageal cancer 1 (DLEC1) is a tumour suppressor gene that is downregulated in various cancers in humans; however, the physiological and molecular functions of DLEC1 are still unclear. This study investigated the critical role of Dlec1 in spermatogenesis and male fertility in mice. Dlec1 was significantly expressed in testes, with dominant expression in germ cells. We disrupted Dlec1 in mice and analysed its function in spermatogenesis and male fertility. Dlec1 deletion caused male infertility due to impaired spermatogenesis. Spermatogenesis progressed normally to step 8 spermatids in Dlec1 mice, but in elongating spermatids, we observed head deformation, a shortened tail, and abnormal manchette organization. These phenotypes were similar to those of various intraflagellar transport (IFT)-associated gene-deficient sperm. In addition, DLEC1 interacted with tailless complex polypeptide 1 ring complex (TRiC) and Bardet-Biedl Syndrome (BBS) protein complex subunits, as well as α- and β-tubulin. DLEC1 expression also enhanced primary cilia formation and cilia length in A549 lung adenocarcinoma cells. These findings suggest that DLEC1 is a possible regulator of IFT and plays an essential role in sperm head and tail formation in mice.
抑癌基因Deleted in lung and esophageal cancer 1（DLEC1）在人类多种癌症中呈下调表达，属于抑癌基因，但 DLEC1 的生理和分子功能仍不清楚。本研究探讨了 Dlec1 在小鼠精子发生和雄性生育力中的关键作用。Dlec1 在睾丸中表达明显，在生殖细胞中优势表达。我们在小鼠中敲除 Dlec1 并分析其在精子发生和雄性生育力中的功能。Dlec1 缺失导致雄性不育，因为精子发生受损。Dlec1 缺失的小鼠精子发生正常进展到 8 期精母细胞，但在伸长的精子中，我们观察到头变形、尾巴缩短和异常顶体小体组织。这些表型与各种鞭毛内运输（IFT）相关基因缺失的精子相似。此外，DLEC1 与无尾复合物多肽 1 环复合物（TRiC）和 Bardet-Biedl 综合征（BBS）蛋白复合物亚基以及α-和β-微管蛋白相互作用。DLEC1 的表达也增强了 A549 肺腺癌细胞中的初级纤毛形成和纤毛长度。这些发现表明，DLEC1 可能是 IFT 的调节剂，在小鼠精子头和尾的形成中发挥重要作用。
