CMTM2 is essential for spermiogenesis in mice

Objective: This study is to investigate whether CKLF-like MARVEL transmembrane domain-containing protein 2 (CMTM2) is involved in spermatogenesis in mice. CMTM2 is highly expressed in testis, and could possibly a potential spermagogenesis specific gene. Methods: CMTM2-deficient mouse model was generated. Northern, RT-PCR and Western blotting analysis were performed on total RNA derived from wild-type (WT, CMTM2+/+) and CMTM2+/(heterozygote) and CMTM2-/(homozygote) mice to examine the CMTM2 level. The number of litters and the number of pups were counted and pregnancy rates calculated. The motility and morphology of the sperm and the histology of testes were analyzed. Serum testosterone and FSH concentrations were also measured. Standard t-tests (Excel, Microsoft, Redmond, WA, USA) were used and standard error of means were calculated. Results: CMTM2 is highly expressed in a finely regulated pattern in the mouse testis during spermatogenesis. The body weight of adult mice with CMTM2 deficiency was not significantly different from that of wild type mice. No obvious anatomical or behavioral abnormalities were observed. The testes of CMTM2-/were smaller than that of CMTM2+/+ mice. Female CMTM2 null mice are fertile, indicating that CMTM2 is not required for female gametogenesis. The CMTM2-/mice produced virtually no sperm, and CMTM2+/mice sperm count showed a significant decline. The hormone levels are not significantly different. The CMTM2-/male mice are sterile due to a late, complete arrest of spermiogenesis. The organized architecture of the seminiferous epithelium of the seminiferous tubules seen in CMTM2+/+ mice was lost in CMTM2-/mice. Conclusions: This study suggests CMTM2 is not required for embryonic development in the mouse but is essential for spermiogenesis.