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MEIG1 is essential for spermiogenesis in mice

机译:MEIG1对小鼠精子发生至关重要

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摘要

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.
机译:精子发生可分为三个阶段:精原细胞的有丝分裂,精细胞的减数分裂和精子发生。在精子发生过程中,精子会发生剧烈的形态变化,包括鞭毛的形成和染色体的包装以及核向精子头的凝结。调节后一过程的基因在很大程度上是未知的。我们先前发现双功能基因Spag16对精子发生必不可少。发现SPAG16S是源自Spag16基因的35 kDa睾丸特异性同工型,被发现与减数分裂表达基因1产物(MEIG1)结合,该产物最初被认为在减数分裂中起作用。我们灭活了Meig1基因,出乎意料的是,发现Meig1突变型雄性小鼠在减数分裂中没有明显缺陷,但是由于在延伸和凝结阶段精子发生受损而变得不育。透射电子显微镜显示,在MEIG1缺陷型小鼠的精细胞中,该精子,精子头和鞭毛形成所必需的微管细胞器被破坏。我们还发现,MEIG1与帕金共同调控基因(PACRG)蛋白相关,并且在MEIG1缺陷小鼠中睾丸PACRG蛋白减少。 PACRG被认为在轴突/鞭毛的组装中起关键作用,Pacrg缺陷型小鼠的生殖表型与Meig1突变型小鼠的表型相似。我们的发现揭示了MEIG1 / PARCG伙伴关系在手杖结构和功能以及精子发生控制中的关键作用。

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    Departments of Obstetrics and Gynecology, Virginia Commonwealth University, Richmond, VA 23298 Departments of Biochemistry, Virginia Commonwealth University, Richmond, VA 23298;

    Departments of Obstetrics and Gynecology, Virginia Commonwealth University, Richmond, VA 23298;

    Departments of Obstetrics and Gynecology, Virginia Commonwealth University, Richmond, VA 23298 Departments of Biochemistry, Virginia Commonwealth University, Richmond, VA 23298;

    Department of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030;

    Department of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030;

    Department of Cell Biology, Center for Research in Contraceptive and Reproductive Health, University of Virginia, 1300 Jefferson Park Avenue, Charlottesville, VA 22908;

    Department of Cell Biology, Center for Research in Contraceptive and Reproductive Health, University of Virginia, 1300 Jefferson Park Avenue, Charlottesville, VA 22908;

    Laboratories of Reproductive and Developmental Toxicology, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709;

    Departments of Obstetrics and Gynecology, Virginia Commonwealth University, Richmond, VA 23298 Departments of Biochemistry, Virginia Commonwealth University, Richmond, VA 23298;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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  • 正文语种 eng
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