Deletion of the initial methionine codon of the Tmem95 gene causes subfertility, but not complete infertility, in male mice.

Abstract

Dear Editor,In mammals, sperm izumo sperm-egg fusion 1 (IZUMO1) and oocyte IZUMO1 receptor (JUNO) interaction plays a pivotal role in the recognition of gametes prior to membrane fusion through multiple intermolecular reactions [1–3]. Although many of the factors involved in gamete fusion have recently been identified, their specific contributions remain largely unknown [1]. Among them, transmembrane protein 95 (TMEM95) was initially identified as a responsible gene for male subfertility in Fleckvieh bulls by a genome-wide association study [4, 5]. Furthermore, in 2020, two research teams reported that CRISPR/Cas9-mediated Tmem95 disruption caused complete sterility in male mice due to gamete fusion failure [6, 7]. In order to analyze the phenotype, we newly produced a TMEM95 knockout mouse line. We designed a single guide RNA to target the initial methionine codon for the Tmem95 gene since this gene has some alternative splicing...