Knockout of the family with sequence similarity 181, member A (Fam181a) gene does not impair spermatogenesis or male fertility in the mouse

Abstract

Family with sequence similarity 181 (Fam181) is a gene family with two paralogues (Fam181a and Fam181b) found among vertebrates. Fam181a exhibits dynamic and stage-specific expression during murine embryo development. Furthermore, searching in the National Center for Biotechnology Information database revealed predominant expression of Fam181a in mouse and human testes, implying that it may have essential roles in spermatogenesis. In this study we investigated the invivo function of Fam181a in mouse spermatogenesis and fertility by generating Fam181a–/– mice using clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated (Cas) 9 genome editing technology. The resulting Fam181a–/– mice exhibited normal growth and development. In addition, the mice were completely fertile, with no obvious differences in the testis-to-bodyweight ratio, epididymal sperm count or sperm motility compared with wild-type mice. Further examination of testicular and epididymal histology of Fam181a–/– mice found an intact seminiferous tubule structure and the presence of all types of germ cells, from spermatogonia to mature spermatozoa, similar to wild-type littermates. Similarly, analysis of meiotic prophase I progression revealed normal populations of each substage of prophase I in Fam181a+/+ and Fam181a–/– testes, suggesting that this gene is dispensable for male fertility. These negative findings will help avoid research overlap, save time and resources and allow researchers to concentrate on genes that are critical for male fertility and spermatogenesis.