title: Male infertility, impaired sperm motility, and hydrocephalus in mice deficient in sperm-associated antigen 6.
abstract: Gene targeting was used to create mice lacking sperm-associated antigen 6 (Spag6), the murine orthologue of Chlamydomonas PF16, an axonemal protein containing eight armadillo repeats predicted to be important for flagellar motility and stability of the axoneme central apparatus. Within 8 weeks of birth, approximately 50% of Spag6-deficient animals died with hydrocephalus. Spag6-deficient males surviving to maturity were infertile. Their sperm had marked motility defects and was morphologically abnormal with frequent loss of the sperm head and disorganization of flagellar structures, including loss of the central pair of microtubules and disorganization of the outer dense fibers and fibrous sheath. We conclude that Spag6 is essential for sperm flagellar motility and that it is important for the maintenance of the structural integrity of mature sperm. The occurrence of hydrocephalus in the mutant mice also implicates Spag6 in the motility of ependymal cilia.
authors.affiliation: Center for Research on Reproduction and Women's Health, University of Pennsylvania Medical Center, Philadelphia, Pennsylvania 19104, USA.
authors.forename: Rossana
authors.initials: R
authors.lastname: Sapiro
authors.forename: Igor
authors.initials: I
authors.lastname: Kostetskii
authors.forename: Patricia
authors.initials: P
authors.lastname: Olds-Clarke
authors.forename: George L
authors.initials: GL
authors.lastname: Gerton
authors.forename: Glenn L
authors.initials: GL
authors.lastname: Radice
authors.forename: Jerome F
authors.initials: JF
authors.lastname: Strauss III
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics; D000818:Animals; D002465:Cell Movement; D002923:Cilia / Q000648:ultrastructure; D004805:Ependyma / Q000473:pathology; D005260:Female; D005838:Genotype; D006130:Growth Disorders / Q000235:genetics; D006849:Hydrocephalus / Q000235:genetics*; D007248:Infertility, Male / Q000235:genetics*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008818:Mice, Neurologic Mutants; D008868:Microtubule Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D008870:Microtubules / Q000648:ultrastructure; D012333:RNA, Messenger / Q000032:analysis; D013077:Sperm Head / Q000648:ultrastructure; D013081:Sperm Motility / Q000235:genetics*; D013082:Sperm Tail / Q000648:ultrastructure; D013094:Spermatozoa / Q000002:abnormalities*; D013737:Testis / Q000737:chemistry
chemical_list: D008868:Microtubule Proteins; D012333:RNA, Messenger; C400106:SPAG6 protein, human