State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Sciences, Fudan University, Shanghai, 200433, P.R. China.
Department of Anatomy and Molecular Embryology, Ruhr-University Bochum, Bochum, Germany.
Sci Rep. 2017 Jun 7;7(1):2998. doi: 10.1038/s41598-017-03193-y.
Gametogenetin Binding Protein 2 (GGNBP2) was identified as a tumor suppressor and verified as such by several studies. GGNBP2 has also been reported to be essential for pregnancy maintenance via regulation of trophoblast stem cells. Gametogenetin (GGN) is a testicular germ cell-specific gene expressed in adult testes. As a potential GGN1-interacting protein, the role of GGNBP2 in spermatogenesis has not yet been clarified. We generated heterozygous GGNBP2 knockout mice and bred them by intercrossing. We found that among the offspring, homozygous GGNBP2 knockout (KO) mice were present in severely reduced numbers. The GGNBP2 KO pups developed normally, but the male siblings showed dramatically reduced fertility. In these male homozygous GGNBP2 KO mice, the only pathological finding was abnormal morphology of the testes and absence of spermatozoa. In addition, increased apoptosis was observed in the testes of GGNBP2 KO mice. SOX9 staining revealed that SOX9-positive Sertoli cells were absent in the seminiferous tubules. In homozygous mice, proliferating cell nuclear antigen (PCNA)-positive cells were localized in the lumen of the convoluted seminiferous tubules. These results suggest that GGNBP2 plays a key role in spermatogenesis by affecting the morphology and function of SOX9-positive Sertoli cells.
配子体基因结合蛋白 2（GGNBP2）被鉴定为一种肿瘤抑制因子，并被多项研究证实。有报道称，GGNBP2 还通过调节滋养层干细胞对妊娠维持至关重要。配子体（GGN）是一种睾丸生殖细胞特异性基因，在成年睾丸中表达。作为一种潜在的 GGN1 相互作用蛋白，GGNBP2 在精子发生中的作用尚未阐明。我们生成了杂合子 GGNBP2 敲除小鼠，并通过杂交繁殖它们。我们发现，在后代中，纯合子 GGNBP2 敲除（KO）小鼠的数量严重减少。GGNBP2 KO 幼鼠正常发育，但雄性同胞的生育能力显著降低。在这些雄性纯合子 GGNBP2 KO 小鼠中，唯一的病理发现是睾丸形态异常和精子缺失。此外，在 GGNBP2 KO 小鼠的睾丸中观察到细胞凋亡增加。SOX9 染色显示，曲细精管中缺乏 SOX9 阳性支持细胞。在纯合子中，增殖细胞核抗原（PCNA）阳性细胞定位于弯曲的曲细精管管腔中。这些结果表明，GGNBP2 通过影响 SOX9 阳性支持细胞的形态和功能，在精子发生中发挥关键作用。
