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Publication : Ggnbp2-Null Mutation in Mice Leads to Male Infertility due to a Defect at the Spermiogenesis Stage.

First Author  Liu L Year  2017
Journal  Am J Pathol Volume  187
Issue  11 Pages  2508-2519
PubMed ID  28823874 Mgi Jnum  J:249037
Mgi Id  MGI:6094314 Doi  10.1016/j.ajpath.2017.07.016
Citation  Liu L, et al. (2017) Ggnbp2-Null Mutation in Mice Leads to Male Infertility due to a Defect at the Spermiogenesis Stage. Am J Pathol 187(11):2508-2519
abstractText  Gametogenetin binding protein 2 (GGNBP2) is an evolutionarily conserved zinc finger protein. Although Ggnbp2-null embryos in the B6 background died because of a defective placenta, 6.8% of Ggnbp2-null mice in the B6/129 mixed background were viable and continued to adulthood. Adult Ggnbp2-null males were sterile, with smaller testes and an azoospermic phenotype, whereas mutant females were fertile. Histopathological analysis of 2-month-old Ggnbp2-null testes revealed absence of mature spermatozoa in the seminiferous tubules and epididymides and reduction of the number of spermatids. Ultrastructural analysis indicated dramatic morphological defects of developing spermatids in the Ggnbp2-null testes, including irregularly shaped acrosomes, acrosome detachment, cytoplasmic remnant, ectopic manchette, and ill-formed head shape in both elongating and elongated spermatids. However, the numbers of spermatogonia, spermatocytes, Leydig cells, and Sertoli cells in Ggnbp2-null testes did not significantly differ from the wild-type siblings. Gonadotropins, testosterone, and the blood-testis barrier were essentially unaffected. Western blot analyses showed increases in alpha-E-catenin, beta-catenin, and N-cadherin, decreases in E-cadherin, afadin, and nectin-3, and no changes in vinculin, nectin-2, focal adhesion kinase, and integrin-beta1 protein levels in Ggnbp2-null testes compared to wild-type siblings. Together, this study demonstrates that GGNBP2 is critically required for maintenance of the adhesion integrity of the adlumenal germ epithelium and is indispensable for normal spermatid transformation into mature spermatozoa in mice.
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