HGNC Approved Gene Symbol: SPAG6
Cytogenetic location: 10p12.2 Genomic coordinates (GRCh38): 10:22,345,496-22,417,610 (from NCBI)
Sperm plasma membrane antigens are attractive antifertility vaccine targets because antibodies to them impair sperm function and have been found in a subset of infertile couples as well as in many vasectomized men in whom infertility has persisted after vasectomy reversal. By immunoscreening a testis cDNA expression library with serum from an infertile male with high levels of antisperm antibodies, Neilson et al. (1999) isolated a cDNA encoding SPAG6. Sequence analysis predicted that the 509-amino acid protein contains 8 contiguous armadillo repeats and is 64% identical to a flagellar protein involved in protein-protein interactions important for central microtubule stability and flagellar motility of Chlamydomonas reinhardtii. Armadillo repeats, named after the Drosophila armadillo protein (see 604275), are highly conserved in length and spacing and are thought to allow a protein to interact with itself or other molecules to form highly ordered 3-dimensional structures. Northern blot analysis revealed expression of 1.8- and 2.8-kb transcripts, consistent with the presence of 2 polyadenlyation sites, only in testis. Southern blot analysis determined that SPAG6 is highly conserved in primates and that a homolog is present in rodents. Western blot analysis showed that SPAG6 is expressed in sperm as a 55-kD protein. Immunocytochemistry demonstrated intracellular expression along sperm tails. Neilson et al. (1999) commented that the antibodies in the infertile male's serum probably arose from leaked protein from damaged sperm cells.
Using FISH, Neilson et al. (1999) mapped the SPAG6 gene to 10p12-p11.2.
Sapiro et al. (2002) found that about 50% of Spag6-deficient mice died with hydrocephalus within 8 weeks of birth. Surviving females were fertile at maturity, but males were not. The sperm of mutant males had marked motility defects and showed morphologic abnormalities, with frequent loss of the sperm head and disorganized flagellar structures, including loss of the central pair of microtubules and disorganized outer dense fibers and fibrous sheath. Sapiro et al. (2002) concluded that SPAG6 is required for the structural integrity of mature sperm and for motility of ependymal cilia.
Neilson, L. I., Schneider, P. A., Van Deerlin, P. G., Kiriakidou, M., Driscoll, D. A., Pellegrini, M. C., Millinder, S., Yamamoto, K. K., French, C. K., Strauss, J. F., III. cDNA cloning and characterization of a human sperm antigen (SPAG6) with homology to the product of the Chlamydomonas PF16 locus. Genomics 60: 272-280, 1999. [PubMed: 10493827] [Full Text: https://doi.org/10.1006/geno.1999.5914]
Sapiro, R., Kostetskii, I., Olds-Clarke, P., Gerton, G. L., Radice, G. L., Strauss, J. F., III. Male infertility, impaired sperm motility, and hydrocephalus in mice deficient in sperm-associated antigen 6. Molec. Cell. Biol. 22: 6298-6305, 2002. [PubMed: 12167721] [Full Text: https://doi.org/10.1128/MCB.22.17.6298-6305.2002]