Identification of Testis-Expressed Cell Cycle Regulating Proteins with Special Reference to Meiosis

Two percent of human males are infertile because of severe defects in sperm production. In the clinical cases spermatogenic arrest is an interruption of germ cell differentiation that may result in either oligozoospermia or azoospermia and can be diagnosed in testicular biopsy. Although spermatogenesis requires many gene products, mutation or absence of the genes expressed at different levels of spermatogenesis may lead to spermatogenic arrest and infertility. Identification of new genes specifically involved in spermatogenesis and analysis of the phenotypes could provide an insight into this developmental process and a more rational basis for treatment of male infertility. Using differential display proteomics followed by genomic assays and molecular modeling, we have identified a few testis-specific genes that may regulate cell cycle in germ cells. We are currently concentrating on a class of testis-specific proteins named Cyclin-Like Proteins (CLPs), which are classical cyclin box-bearing proteins with typical folds. Using RT-PCR based approach, we have sequenced the full length CDS of mouse testicular CLP-1. With major thrust on this molecule, we are aiming at elucidating the intricate molecular control of meiosis and germ cell differentiation. We will also attempt to examine whether there are defects in the CDS of CLP-1 gene associated with male subfertility.