title: MEIG1 is essential for spermiogenesis in mice.
abstract: Spermatogenesis can be divided into three stages: spermatogonial mitosis, meiosis of spermatocytes, and spermiogenesis. During spermiogenesis, spermatids undergo dramatic morphological changes including formation of a flagellum and chromosomal packaging and condensation of the nucleus into the sperm head. The genes regulating the latter processes are largely unknown. We previously discovered that a bi-functional gene, Spag16, is essential for spermatogenesis. SPAG16S, the 35 kDa, testis-specific isoform derived from the Spag16 gene, was found to bind to meiosis expressed gene 1 product (MEIG1), a protein originally thought to play a role in meiosis. We inactivated the Meig1 gene and, unexpectedly, found that Meig1 mutant male mice had no obvious defect in meiosis, but were sterile as a result of impaired spermatogenesis at the stage of elongation and condensation. Transmission electron microscopy revealed that the manchette, a microtubular organelle essential for sperm head and flagellar formation was disrupted in spermatids of MEIG1-deficient mice. We also found that MEIG1 associates with the Parkin co-regulated gene (PACRG) protein, and that testicular PACRG protein is reduced in MEIG1-deficient mice. PACRG is thought to play a key role in assembly of the axonemes/flagella and the reproductive phenotype of Pacrg-deficient mice mirrors that of the Meig1 mutant mice. Our findings reveal a critical role for the MEIG1/PARCG partnership in manchette structure and function and the control of spermiogenesis.
authors.affiliation: Departments of Obstetrics and Gynecology and Biochemistry, Virginia Commonwealth University, Richmond, VA 23298, USA. zzhang4@vcu.edu
authors.forename: Zhibing
authors.initials: Z
authors.lastname: Zhang
authors.forename: Xuening
authors.initials: X
authors.lastname: Shen
authors.forename: David R
authors.initials: DR
authors.lastname: Gude
authors.forename: Bonney M
authors.initials: BM
authors.lastname: Wilkinson
authors.forename: Monica J
authors.initials: MJ
authors.lastname: Justice
authors.forename: Charles J
authors.initials: CJ
authors.lastname: Flickinger
authors.forename: John C
authors.initials: JC
authors.lastname: Herr
authors.forename: Edward M
authors.initials: EM
authors.lastname: Eddy
authors.forename: Jerome F
authors.initials: JF
authors.lastname: Strauss
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D015153:Blotting, Western; D019556:COS Cells; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D002522:Chlorocebus aethiops; D004268:DNA-Binding Proteins; D020043:Genes, Essential; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D047468:Immunoprecipitation; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008840:Microfilament Proteins; D008854:Microscopy, Electron; D018832:Molecular Chaperones; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D021381:Protein Transport; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid; D013087:Spermatids / Q000378:metabolism / Q000502:physiology* / Q000648:ultrastructure; D013091:Spermatogenesis / Q000235:genetics / Q000502:physiology*; D013737:Testis / Q000166:cytology / Q000378:metabolism / Q000648:ultrastructure; D020798:Two-Hybrid System Techniques
chemical_list: D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; C500770:Meig1 protein, mouse; D008840:Microfilament Proteins; D018832:Molecular Chaperones; D009687:Nuclear Proteins; C471712:Pacrg protein, mouse; D010750:Phosphoproteins; D011506:Proteins; C489505:Tnp2 protein, mouse; D049452:Green Fluorescent Proteins