title: Mice expressing aberrant sperm-specific protein PMIS2 produce normal-looking but fertilization-incompetent spermatozoa.
abstract: Eight kinds of gene-disrupted mice (Clgn, Calr3, Pdilt, Tpst2, Ace, Adam1a, Adam2, and Adam3) show impaired sperm transition into the oviducts and defective sperm binding to the zona pellucida. All of these knockout strains are reported to lack or show aberrant expression of a disintegrin and metallopeptidase domain 3 (ADAM3) on the sperm membrane. We performed proteomic analyses of the proteins of these infertile spermatozoa to clarify whether the abnormal function is caused exclusively by a deficiency in ADAM3 expression. Two proteins, named PMIS1 and PMIS2, were missing in spermatozoa from Clgn-disrupted mice. To study their roles, we generated two gene-disrupted mouse lines. Pmis1-knockout mice were fertile, but Pmis2-knockout males were sterile because of a failure of sperm transport into the oviducts. Pmis2-deficient spermatozoa also failed to bind to the zona pellucida. However, they showed normal fertilizing ability when eggs surrounded with cumulus cells were used for in vitro fertilization. Further analysis revealed that these spermatozoa lacked the ADAM3 protein, but the amount of PMIS2 was also severely reduced in Adam3-deficient spermatozoa. These results suggest that PMIS2 might function both as the ultimate factor regulating sperm transport into the oviducts and in modulating sperm-zona binding.
authors.affiliation: Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, Japan.
authors.forename: Ryo
authors.initials: R
authors.lastname: Yamaguchi
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Fujihara
authors.forename: Masahito
authors.initials: M
authors.lastname: Ikawa
authors.forename: Masaru
authors.initials: M
authors.lastname: Okabe
mesh_terms: D051722:ADAM Proteins / Q000235:genetics; D000818:Animals; D002135:Calcium-Binding Proteins / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics; D002460:Cell Line; D005306:Fertilization; D007248:Infertility, Male / Q000235:genetics; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D018832:Molecular Chaperones / Q000096:biosynthesis / Q000235:genetics; D011506:Proteins / Q000235:genetics* / Q000378:metabolism*; D013084:Sperm-Ovum Interactions / Q000235:genetics / Q000502:physiology; D013094:Spermatozoa / Q000378:metabolism* / Q000502:physiology; D015044:Zona Pellucida / Q000378:metabolism
chemical_list: D002135:Calcium-Binding Proteins; D008562:Membrane Glycoproteins; D018832:Molecular Chaperones; C576740:PMIS1 protein, mouse; C576741:PMIS2 protein, mouse; D011506:Proteins; C087341:calmegin; D051722:ADAM Proteins; C485429:Adam3 protein, mouse