Human cyritestin genes (CYRN1 and CYRN2) are non-functional

The mouse cyritestin gene is a member of the ADAM ( a disintegrin and metal loprotease) gene family and codes for a membrane-anchored sperm protein. Re cently, it was shown that cyritestin is critical for male fertility in the mouse. Spermatozoa of cyritestin-deficient mice are not able to bind to the zona pellucida of the oocyte and therefore unable to fertilize the egg. Ho wever, zona-free oocytes can be fertilized and the resulting embryos show n ormal development. In contrast to the mouse, where only one gene for cyrite stin (Cyrn) is reported, two cyritestin genes (CYRN1 and CYRN2) are known i n humans. The human CYRN1 and CYRN2 genes are located on chromosomes 8 and 16, respectively. We report that 27 % of fertile men are deficient for the CYRN1 gene but that all have a CYRN2 gene, suggesting that the CYRN2 gene i s the orthologous mouse cyritestin gene in humans and might be involved in sperm-egg interactions. However, the characterization of CYRN2 transcripts from testicular RNA of CYRN1-deficient men demonstrated many termination co dons in the synthesized cyritestin cDNA. Furthermore, Western-blot analysis with human testicular protein extracts using an anti-cyritestin antibody f ailed to detect any cyritestin protein. These results demonstrate clearly t hat both cyritestin genes are non-functional in humans.