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Deficiency of SPAG16L Causes Male Infertility Associated with Impaired Sperm Motility¹

Center for Research on Reproduction and Women's Health,³ Department of Ophthalmology,⁴ University of Pennsylvania Medical Center, Philadelphia, Pennsylvania, 19104 Department of Histology and Embryology,⁵ University of the Republic, CP 11800 Montevideo, Uruguay Department of Obstetrics and Gynecology,⁶ Virginia Commonwealth University, Richmond, Virginia, 23298

ABSTRACT

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_r 71 x 10³ (SPAG16L) and M_r 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.

gamete biology, sperm, sperm motility and transport, testis

¹ Supported by National Institutes of Health grants HD37416, HD06724, and TW06223–01, and the Foundation Fighting Blindness (FFB).

² Correspondence: Jerome F. Strauss, III, School of Medicine, Virginia Commonwealth University, Sanger Hall, 1101 East Marshall Street, Room 1–071, P.O. Box 980565, Richmond, VA 23298. FAX: 804 828 7628; e-mail:jfstrauss{at}vcu.edu

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