Chromatin remodelling in spermatids is an essential step in spermiogenesis and involves the exchange of most histones by protamines, which drives chromatin condensation in late spermatids. The gene Rimklb encodes a citrylglutamate synthase highly expressed in testes of vertebrates and the increase of its reaction product, β-citrylglutamate, correlates in time with the appearance of spermatids. Here we show that deficiency in a functional Rimklb gene leads to male subfertility, which could be partially rescued by in vitro fertilization. Rimklb-deficient mice are impaired in a late step of spermiogenesis and produce spermatozoa with abnormally shaped heads and nuclei. Sperm chromatin in Rimklb-deficient mice was less condensed and showed impaired histone to protamine exchange and retained transition protein 2. These observations suggest that citrylglutamate synthase, probably via its reaction product β-citrylglutamate, is essential for efficient chromatin remodelling during spermiogenesis and may be a possible candidate gene for male subfertility or infertility in humans.
Citrylglutamate synthase deficient male mice are subfertile with impaired histone and transition protein 2 removal in late spermatids
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Lihua Wang-Eckhardt, Marc Sylvester, Ivonne Becker, Jean-Pierre Allam, Matthias Eckhardt; Citrylglutamate synthase deficient male mice are subfertile with impaired histone and transition protein 2 removal in late spermatids. Biochem J 13 May 2022; 479 (9): 953–972. doi: https://doi.org/10.1042/BCJ20210844
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