Deficiency of SPAG16L Causes Male Infertility Associated with Impaired Sperm Motility

• Published in: Biology of reproduction Vol. 74; no. 4; pp. 751 - 759
• Main Authors: Zhang, Zhibing, Kostetskii, Igor, Tang, Waixing, Haig-Ladewig, Lisa, Sapiro, Rossana, Wei, Zhangyong, Patel, Aatish M, Bennett, Jean, Gerton, George L, Moss, Stuart B, Radice, Glenn L, Strauss, Jerome F. III
• Format: Journal Article
• Language: English
• Published: Madison, WI Society for the Study of Reproduction, Inc 01.04.2006; Society for the Study of Reproduction
• Subjects: Animals; Biological and medical sciences; Chlamydomonas; Female; Fertility; Fundamental and applied biological sciences. Psychology; Germ Cells - transplantation; Infertility, Male - etiology; Infertility, Male - physiopathology; Male; Mammalia; Mammalian male genital system; Mice; Microtubule-Associated Proteins - deficiency; Microtubule-Associated Proteins - genetics; Morphology. Physiology; Mutagenesis, Insertional; Sperm Motility; Spermatogenesis; Spermatozoa - ultrastructure; Testis - anatomy & histology; Vertebrates: reproduction; Spermatozoa; sperm motility and transport; Motility; Biological transport; gamete biology; sperm; testis; Germinal cell; Testicle; Male genital system; Gamete; Reproduction; Male sterility; Male genital diseases
• ISSN: 0006-3363; 1529-7268
• DOI: 10.1095/biolreprod.105.049254

The axonemes of cilia and flagella contain a "9+2" structure of microtubules and associated proteins. Proteins associated with the central doublet pair have been identified in Chlamydomonas that result in motility defects when mutated. The murine orthologue of the Chlamydomonas PF20 gene, sperm-associated antigen 16 (Spag16), encodes two proteins of M[subscript r] [approximately]71 x 10³ (SPAG16L) and M[subscript r] [approximately]35 x 10³ (SPAG16S). In sperm, SPAG16L is found in the central apparatus of the axoneme. To determine the function of SPAG16L, gene targeting was used to generate mice lacking this protein but still expressing SPAG16S. Mutant animals were viable and showed no evidence of hydrocephalus, lateralization defects, sinusitis, bronchial infection, or cystic kidneys--symptoms typically associated with ciliary defects. However, males were infertile with a lower than normal sperm count. The sperm had marked motility defects, even though ultrastructural abnormalities of the axoneme were not evident. In addition, the testes of some nullizygous animals showed a spermatogenetic defect, which consisted of degenerated germ cells in the seminiferous tubules. We conclude that SPAG16L is essential for sperm flagellar function. The sperm defect is consistent with the motility phenotype of the Pf20 mutants of Chlamydomonas, but morphologically different in that the mutant algal axoneme lacks the central apparatus.