Wang Mengyue, Li Jiayi, Liu Bowen, Shen Zhiming, Chen Min, Cui Xiuhong, Liu Hongbin, Gao Fei, Zhao Han
State Key Laboratory of Reproductive Medicine and Offspring Health, Center for Reproductive Medicine, Institute of Women, Children and Reproductive Health, Shandong University, Jinan, China.
National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Shandong University, Jinan, China.
Cell Prolif. 2025 Jun;58(6):e13810. doi: 10.1111/cpr.13810. Epub 2025 Jan 26.
TRAPPC2L is a core subunit of the Transport Protein Particle (TRAPP) complex, which is involved in vesicle transport and autophagy. Mutations in Trappc2l gene are associated with neurodevelopmental disorders, characterised by severe neurodevelopmental delays and varying degrees of muscle abnormalities. In this study, we found that the knockout of Trappc2l did not cause developmental abnormalities in both male and female mice. However, the male mice were completely infertile. Histological examination revealed that germ cell syncytial structures with multiple nuclear were formed in Trappc2l knockout mice from embryonic day 17.5 (E17.5) and the number and size of these structures gradually were increased at later developmental stages. The germ cells were completely lost at 2 weeks after birth. Further study found that germ cell syncytial structures were most likely formed by abnormal cell division but not cell fusion. We also found that meiosis-associated genes Stra8 and Sycp3 were expressed in Trappc2l-deficient germ cells during the embryonic stage. Our study demonstrated that Trappc2l is essential for germ cell development in male mice which is probably involved in keeping the mitotic quiescent state of male germ cells during the embryonic stage.
TRAPPC2L是转运蛋白颗粒(TRAPP)复合体的一个核心亚基,该复合体参与囊泡运输和自噬过程。Trappc2l基因的突变与神经发育障碍有关,其特征为严重的神经发育迟缓以及不同程度的肌肉异常。在本研究中,我们发现敲除Trappc2l基因在雄性和雌性小鼠中均未导致发育异常。然而,雄性小鼠完全不育。组织学检查显示,从胚胎第17.5天(E17.5)起,Trappc2l基因敲除小鼠中形成了具有多个细胞核的生殖细胞合胞体结构,并且这些结构的数量和大小在随后的发育阶段逐渐增加。出生后2周时生殖细胞完全消失。进一步研究发现,生殖细胞合胞体结构很可能是由异常细胞分裂而非细胞融合形成的。我们还发现,减数分裂相关基因Stra8和Sycp3在胚胎期Trappc2l基因缺陷的生殖细胞中表达。我们的研究表明,Trappc2l对于雄性小鼠生殖细胞发育至关重要,这可能与在胚胎期维持雄性生殖细胞的有丝分裂静止状态有关。