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.

中文翻译：

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缺乏柠檬酰谷氨酸合成酶的雄性小鼠不育，晚期精子细胞中组蛋白和过渡蛋白 2 去除受损

精子细胞中的染色质重塑是精子发生的重要步骤，涉及大多数组蛋白与鱼精蛋白的交换，后者驱动晚期精子细胞中的染色质凝聚。Rimklb基因编码一种在脊椎动物睾丸中高度表达的柠檬酰谷氨酸合酶，其反应产物β-柠檬酰谷氨酸的增加与精子细胞的出现及时相关。在这里，我们显示功能性 Rimklb 基因的缺陷导致男性生育能力低下，这可以通过体外受精部分挽救。Rimklb 缺陷小鼠在精子发生的晚期阶段受损，并产生具有异常形状的头部和细胞核的精子。Rimklb 缺陷小鼠的精子染色质浓缩程度较低，组蛋白与鱼精蛋白的交换受损并保留了过渡蛋白 2。