title: MNS1 is essential for spermiogenesis and motile ciliary functions in mice.
abstract: During spermiogenesis, haploid round spermatids undergo dramatic cell differentiation and morphogenesis to give rise to mature spermatozoa for fertilization, including nuclear elongation, chromatin remodeling, acrosome formation, and development of flagella. The molecular mechanisms underlining these fundamental processes remain poorly understood. Here, we report that MNS1, a coiled-coil protein of unknown function, is essential for spermiogenesis. We find that MNS1 is expressed in the germ cells in the testes and localizes to sperm flagella in a detergent-resistant manner, indicating that it is an integral component of flagella. MNS1-deficient males are sterile, as they exhibit a sharp reduction in sperm production and the remnant sperm are immotile with abnormal short tails. In MNS1-deficient sperm flagella, the characteristic arrangement of "9+2" microtubules and outer dense fibers are completely disrupted. In addition, MNS1-deficient mice display situs inversus and hydrocephalus. MNS1-deficient tracheal motile cilia lack some outer dynein arms in the axoneme. Moreover, MNS1 monomers interact with each other and are able to form polymers in cultured somatic cells. These results demonstrate that MNS1 is essential for spermiogenesis, the assembly of sperm flagella, and motile ciliary functions.
authors.affiliation: Department of Animal Biology, Center for Animal Transgenesis and Germ Cell Research, University of Pennsylvania School of Veterinary Medicine, Philadelphia, Pennsylvania, United States of America.
authors.forename: Jian
authors.initials: J
authors.lastname: Zhou
authors.forename: Fang
authors.initials: F
authors.lastname: Yang
authors.forename: N Adrian
authors.initials: NA
authors.lastname: Leu
authors.forename: P Jeremy
authors.initials: PJ
authors.lastname: Wang
mesh_terms: D000818:Animals; D018797:Cell Cycle Proteins; D002478:Cells, Cultured; D002923:Cilia / Q000235:genetics / Q000502:physiology; D005298:Fertility / Q000235:genetics; D005854:Germ Cells / Q000166:cytology / Q000378:metabolism; D006849:Hydrocephalus / Q000235:genetics; D008297:Male; D051379:Mice; D009687:Nuclear Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D013082:Sperm Tail / Q000378:metabolism; D013087:Spermatids / Q000166:cytology / Q000254:growth & development; D013091:Spermatogenesis / Q000235:genetics* / Q000502:physiology; D013094:Spermatozoa / Q000166:cytology / Q000254:growth & development; D014132:Trachea / Q000166:cytology / Q000378:metabolism
chemical_list: D018797:Cell Cycle Proteins; C088400:Mns1 protein, mouse; D009687:Nuclear Proteins