Mfsd14a (Hiat1) gene disruption causes globozoospermia and infertility in male mice
Mfsd14a (Hiat1) gene disruption causes globozoospermia and infertility in male mice
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DOI：
10.1530/rep-15-0557
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发表时间：
2016-07-01
期刊：
影响因子：
3.8
通讯作者：
Colledge, William Henry
中科院分区：
文献类型：
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作者：
Doran, Joanne;Walters, Cara;Colledge, William Henry
Mfsd14a 基因以前称为 Hiat1，编码一种功能未知的跨膜蛋白，与溶质载体蛋白家族同源。为了研究 MFSD14A 蛋白的功能，我们制备了 Mfsd14a 基因被 LacZ 报告基因破坏的突变小鼠（小家鼠，品系 129S6Sv/Ev）。纯合突变小鼠可以存活且健康，但雄性小鼠由于输精管中精子数量减少 100 倍而无法生育。雄性小鼠具有足够水平的睾酮并表现出正常的交配行为。形成的少数精子表现出圆形头部缺陷，类似于在患有球形精子症的人类中发现的缺陷。精子发生正常进行到圆形精子细胞阶段，但随后与精子发生相关的结构变化因顶体形成失败、精子头部凝结和线粒体定位到精子中部而受到严重破坏。作为 Mfsd14a 表达替代物的 β-半乳糖苷酶活性染色表明支持细胞中的表达，表明 MFSD14A 可能从血流中转运精子发生所需的溶质。
The Mfsd14a gene, previously called Hiat1, encodes a transmembrane protein of unknown function with homology to the solute carrier protein family. To study the function of the MFSD14A protein, mutant mice (Mus musculus, strain 129S6Sv/Ev) were generated with the Mfsd14a gene disrupted with a LacZ reporter gene. Homozygous mutant mice are viable and healthy, but males are sterile due to a 100-fold reduction in the number of spermatozoa in the vas deferens. Male mice have adequate levels of testosterone and show normal copulatory behaviour. The few spermatozoa that are formed show rounded head defects similar to those found in humans with globozoospermia. Spermatogenesis proceeds normally up to the round spermatid stage, but the subsequent structural changes associated with spermiogenesis are severely disrupted with failure of acrosome formation, sperm head condensation and mitochondrial localization to the mid-piece of the sperm. Staining for beta-galactosidase activity as a surrogate for Mfsd14a expression indicates expression in Sertoli cells, suggesting that MFSD14A may transport a solute from the bloodstream that is required for spermiogenesis.