Lin Siyuan, Yang Min, Zhu Weipeng, Yang Changqi, Chen Yaosheng, Cong Peiqing, Liu Xiaohong, He Zuyong
State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, 510006, China.
Biol Res. 2025 May 13;58(1):28. doi: 10.1186/s40659-025-00609-2.
A splice mutation that causes skipping of exon 17 in the KIT gene is a major reason for the dominant white phenotype of pigs. Exon 17 of the KIT gene may be related to differences in testis size and sperm quality among different pig breeds. Investigating the effects of exon 17 of the KIT gene on spermatogonia differentiation and testicular development is essential for understanding the genetic causes of reduced fertility and semen quality in pigs. To better understand the effects of the splice mutation of KIT on porcine spermatogenesis, we described an exon 17 deletion mouse model (Kit ) constructed by simulating splice mutations in KIT for functional verification.
Deletion of exon 17 of Kit severely impaired the differentiation of spermatogonia and promoted the apoptosis of germ cells, resulting in testicular dysplasia and decreased sperm quality and male fertility. Further transcriptomic analysis revealed inhibited expression of genes involved in meiosis and spermatogenesis and attenuated MAPK-ERK signaling in the testicular tissues of Kit mice. The attenuated MAPK-ERK signaling caused by impaired Kit phosphorylation was confirmed by western blotting.
Our study demonstrated that deletion of exon 17 of Kit severely impaired spermatogenesis and testicular development, leading to decreased semen quality and male fertility. These findings verified the function of exon 17 in the Kit gene and provide a theoretical basis for improving the semen quality of dominant white pigs through correction of the splice mutation of KIT.
导致KIT基因外显子17跳跃的剪接突变是猪显性白色表型的主要原因。KIT基因的外显子17可能与不同猪品种睾丸大小和精子质量的差异有关。研究KIT基因外显子17对精原细胞分化和睾丸发育的影响，对于理解猪繁殖力和精液质量下降的遗传原因至关重要。为了更好地理解KIT剪接突变对猪精子发生的影响，我们描述了一种通过模拟KIT中的剪接突变构建的外显子17缺失小鼠模型（KitΔ17）用于功能验证。
Kit外显子17的缺失严重损害了精原细胞的分化，并促进了生殖细胞的凋亡，导致睾丸发育不良、精子质量下降和雄性生育力降低。进一步的转录组分析显示，KitΔ17小鼠睾丸组织中参与减数分裂和精子发生的基因表达受到抑制，MAPK-ERK信号减弱。Western印迹证实了由Kit磷酸化受损引起的MAPK-ERK信号减弱。
我们的研究表明，Kit外显子17的缺失严重损害了精子发生和睾丸发育，导致精液质量和雄性生育力下降。这些发现验证了Kit基因中外显子17的功能，并为通过纠正KIT的剪接突变来提高显性白猪的精液质量提供了理论依据。
