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Inactivation of testis-specific gene C4orf46 is dispensable for spermatogenesis and fertility in mouse
Mammalian Genome ( IF 2.7 ) Pub Date : 2021-06-02 , DOI: 10.1007/s00335-021-09879-z
Basit Shah 1 , Ranjha Khan 1 , Wasim Shah 1 , Ayesha Aftab 2 , Manan Khan 3 , Sobia Dil 1 , Qinghua Shi 1
Affiliation  

Several genes have been reported to be involved in spermatogenesis but their functional importance in male fertility is yet needed to be elucidated. Therefore, in current research, we focused to explore the in vivo role of evolutionary conserved and testis-specifically expressed, C4orf46, gene in male mouse fertility and spermatogenesis. The expression profile of C4orf46 is specific to testes and expressed in testes from 7 days of postpartum to onward. Thus, we generated the C4orf46 knockout mice by utilizing CRISPR/Cas9 genome editing technology and examined gene function in spermatogenesis and fertility. Surprisingly, C4orf46 knockout mice were completely fertile, displayed normal testes morphology, however, higher sperm contents were observed in knockout mice compared to wild type (WT) littermates. Subsequently, intact testis histology and architecture of seminiferous tubules were observed in C4orf46 knockout and WT mice. Similarly, sperm morphology and swimming velocity of C4orf46 knockout mice were comparable with the WT littermates. Furthermore, all type of germ cells ranging from spermatogonia to mature spermatozoa were observed in the testes and epididymis sections of C4orf46 knockout mice suggesting that disruption of C4orf46 did not impact spermatogenesis. Moreover, meiotic prophase I progression was normal, and each type of cell population was comparable between knockout and WT mice. Overall, finding from this research indicates that C4orf46 is not an essential gene for fertility in mice. This study will help researchers to avoid the repetition and duplication of efforts, and to explore the genes that are indispensable for spermatogenesis and male fertility.



中文翻译:

睾丸特异性基因 C4orf46 的失活对于小鼠精子发生和生育能力是必不可少的

据报道,一些基因与精子发生有关,但它们在男性生育能力中的功能重要性仍有待阐明。因此,在当前的研究中,我们重点探讨进化保守且睾丸特异性表达的C4orf46基因在雄性小鼠生育力和精子发生中的体内作用。C4orf46的表达谱是睾丸特有的,从产后 7 天开始一​​直在睾丸中表达。因此,我们利用CRISPR/Cas9基因组编辑技术制备了C4orf46基因敲除小鼠,并检测了基因在精子发生和生育能力中的功能。令人惊讶的是,C4orf46基因敲除小鼠完全具有生育能力,表现出正常的睾丸形态,然而,与野生型(WT)同窝小鼠相比,基因敲除小鼠的精子含量更高。随后,在C4orf46敲除小鼠和 WT 小鼠中观察到完整的睾丸组织学和曲细精管结构。同样,C4orf46敲除小鼠的精子形态和游泳速度与 WT 同窝小鼠相当。此外,在C4orf46敲除小鼠的睾丸和附睾切片中观察到从精原细胞到成熟精子的所有类型的生殖细胞,表明C4orf46的破坏不影响精子发生。此外,减数分裂前期 I 进展正常,每种类型的细胞群在敲除小鼠和 WT 小鼠之间具有可比性。总的来说,这项研究的结果表明,C4orf46并不是小鼠生育能力的必需基因。这项研究将帮助研究人员避免重复和重复的努力,并探索精子发生和男性生育能力所必需的基因。

更新日期:2021-06-02
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