Co-expression of sperm membrane proteins CMTM2A and CMTM2B is essential for ADAM3 localization and male fertility in mice

Abstract

Chemokines are signaling proteins that are secreted to induce chemotaxis during an immunological response. However, the functions of transmembrane-type chemokine-like factor (CKLF) and the CMTM (CKLF-like MARVEL transmembrane domain containing) protein family remain to be determined. In this study, we focused on the testis-specific mouse CMTM gene cluster (, and) and generated CRISPR/Cas9-mediated mutant mice to examine their physiological functions. Although mutant mice were fertile, and double mutant mice had defects in male fertility due to impaired sperm function. We found that co-expression of sperm membrane proteins CMTM2A and CMTM2B is required for male fertility and affects the localization of the sperm membrane protein ADAM3 in regulating sperm fertilizing ability.

An update of the regulatory factors of sperm migration from the uterus into the oviduct by genetically manipulated mice

“…indeed affected the localization of ADAM3 (Fujihara, Oji, et al, 2018), which is essential for male fertility (Okabe, 2018). Interestingly, CMTM2B disappeared from sperm in Adam3-deficient mice, while CMTM2A remained.…”

“…Cmtm1 mutant males were fertile, Cmtm2a and Cmtm2b double mutant male mice were sterile due to impaired sperm function (Fujihara, Oji, et al, 2018). Immunostaining indicated that CMTM2A and CMTM2B were localized to the plasma membrane on the sperm head (Fujihara, Oji, et al, 2018).…”

“…In this cluster, the testis‐specific enriched genes Cmtm1 and Cmtm2 were identified in humans, and Cmtm1 , Cmtm2a , and Cmtm2b were present in mice (Li et al, ; Shi et al, ; Wang et al, ). To examine the physiological roles of these genes, Fujihara, Oji, Kojima‐Kita, Larasati, and Ikawa () generated CRISPR/Cas9‐mediated mutant mouse strains. Although Cmtm1 mutant males were fertile, Cmtm2a and Cmtm2b double mutant male mice were sterile due to impaired sperm function (Fujihara, Oji, et al, 2018).…”

“…In this cluster, the testis-specific enriched genes Cmtm1 and Cmtm2 were identified in humans, and Cmtm1, Cmtm2a, and Cmtm2b were present in mice (Li et al, 2006;Shi et al, 2005;Wang et al, 2004). To examine the physiological roles of these genes, Fujihara, Oji, Kojima-Kita, Larasati, and Ikawa (2018) generated CRISPR/Cas9-mediated mutant mouse strains. Although…”

“…Cmtm1 mutant males were fertile, Cmtm2a and Cmtm2b double mutant male mice were sterile due to impaired sperm function (Fujihara, Oji, et al, 2018). Immunostaining indicated that CMTM2A and CMTM2B were localized to the plasma membrane on the sperm head (Fujihara, Oji, et al, 2018). There is also a high similarity of genomic localization and the amino acid sequence among mouse F I G U R E 8 The involvement of the PRSS proteases at each step of spermatogenesis and maturation in male reproductive organs and the sperm journey into the female genital tract.…”