N-myristoyltransferase 1, a key gene for protein N-myristoylation, is dispensable for fertility in male mice.

Abstract

N-Myristoyltransferase 1 (NMT1), the predominant enzyme catalyzing myristoylation of proteins, is involved in various biological processes, including early embryonic development, immune responses, apoptosis, cellular homeostasis, tumorigenesis, and infection, with therapeutic potential in viral and parasitic infections as well as cancer. Despite the critical functions of NMT1, there have been no reports to date regarding its role in reproduction, especially in spermatogenesis. To investigate the function of NMT1 in this context, we utilized CRISPR/Cas9 technology to create a germ cell-specific Nmt1 knockout mice model for the first time. Surprisingly, male mice lacking NMT1 maintained fertility, exhibiting normal testicular structure and sperm morphology, with no significant differences in spermatogenic tubule structure or germ cell distribution compared to wild-type mice. Additionally, the Nmt1^f/f; Stra8-Cre male mice showed no notable defects in meiosis. These findings suggest that NMT1 is not critical for spermatogenesis or male fertility in mice. However, further studies have shown that the compensatory role of NMT2 may play an unexpected role in maintaining myristoylation levels, which provides a new perspective for understanding the role of myristoylation in spermatogenesis.