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.