Identification and characteristics of the testes-specific gene, Ccdc38, in mice

Abstract

Abstract. Distinguishing the testes-specific genes in different species may disclose key genes associated with testes-specific functions and provide sufficient information for the study and treatment of male infertility. A testes-specific gene, coiled-coil domain containing 38 (Ccdc38), was identified by screening UniGene libraries. Systematic bioinformatics analysis demonstrated that the CCDC38 protein was conserved in various mammalian species. It was determined that CCDC38 was exclusively expressed in testes and its expression increased from 2-8 weeks of age. Additional immunohistochemical analysis indicated that CCDC38 was mainly expressed in spermatogonia and spermatocytes. It is of note that, immunofluorescence and co-immunoprecipitation assays demonstrated that CCDC38 interacted with ubiquitinated histone H2A in mouse testes. Therefore, these results suggest that Ccdc38 is a testes-specific gene, which may be important for mouse spermatogenesis. IntroductionInfertility affects ~15% of couples worldwide, with half of cases reported to be due to the male partner (1). Treatments for male infertility have not been developed as the associated molecular mechanisms are not well understood (2). A more detailed investigation of the physiological mechanisms of spermatogenesis is required for an improved understanding of infertility prior to the development of therapies for this condition.Spermatogenesis is a complicated developmental process. Spermatogonia differentiate into spermatocytes and spermatids during two meiotic divisions, which leads to the production of mature sperm (3). Defects at any stage of this process may lead to infertility. The process involves various genes, which encode proteins that in turn are important for specific stages of germ cell development. Theses genes are primarily expressed in spermatogenic cells, and are regulated at the transcriptional or post-transcriptional level. The identification of germ cell-specific or testes-specific genes involved in these unique events provides a means by which to dissect the differentiation program and to study the mechanisms of spermatogenesis. Previous studies have identified a number of testes-specific genes in humans and mice, including fibronectin type 3 and ankyrin repeat domains 1 (4), A kinase (PRKA) anchor protein 3 (5), protein lifeguard 5 (6), protease, serine 41 (7), spermatogenesis associated 33 (2) and testis-specific serine kinase 4 (8). In addition to the aforementioned genes it is possible that additional testis-specific genes exist and provide unique functions.Coiled-coil domain containing 38 (Ccdc38) was selected from the expressed sequence tags (ESTs) obtained through the comparison of testes gene libraries with the libraries of other tissues and cell lines using the differential digital display program (9). The EST profile of Ccdc38 in Unigene (Mm.477086) indicates that the Ccdc38 transcript is detected solely in murine testes, which is consistent with the report at BioGPS.org (10). Ccdc38 orthologs are present in other species, i...

The Functionally Unannotated Proteome of Human Male Tissues: A Shared Resource to Uncover New Protein Functions Associated with Reproductive Biology

“…We performed a survey of the literature published on these 412 uPE1 proteins using various search engines and could find a publication reporting the location of TEX33 in the mouse male germ cell lineage . We also found publications reporting functional roles for CCDC38, CFAP70, CFAP58, and C3orf62 (further discussed in this study) in spermatogenesis, and for ANKDR45 in cell proliferation (Table ). The five latter proteins should no longer be considered as “uPE1” according to neXtProt criteria.…”

Ccdc38is required for sperm flagellum biogenesis and male fertility in mouse

“…Ccdc38 is a testis specific expression gene (Lin et al, 2016), but its role during spermiogenesis has not been investigated yet. In order to study its role during spermiogenesis, we generated Ccdc38 -/mouse model.…”

“…1A). CCDC38, reported as a testisspecific protein (Lin et al, 2016), was chosen first. Epitope-tagged CCDC42 and CCDC38 expressed in HEK293T cells followed by immunoprecipitation experiments demonstrated that CCDC38 was detected in anti-MYC immunoprecipitates from CCDC42 co-transfectants, but not from cells co-transfected with the control plasmid (Fig.…”