GENE EXPRESSION PATTERNS DURING SPERMATOGENESIS

精子发生过程中的基因表达模式

• 批准号: 7610364
• 负责人: CAROL C LINDER
• 金额: $ 5.19万
• 依托单位: NEW MEXICO STATE UNIVERSITY LAS CRUCES
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-05-01 至 2008-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7610364
• 关键词: Apoptosis; Autoantigens; Candidate Disease Gene; Chemicals; Computer Retrieval of Information on Scientific Projects Database; DNA Sequence; Data; Defect; Development; Ethylnitrosourea; Fertilization in Vitro; Funding; Gene Expression; Genes; Genetic; Genome; Germ Cells; Golgi Apparatus; Grant; Head; Homozygote; Human; Infertility; Inherited; Institution; Maps; Meiosis; Mitosis; Mus; Mutagens; Mutation; Pathway interactions; Pattern; Phenotype; Play; Point Mutation; Protein Family; Proteins; Recombinants; Regulation; Reproduction; Research; Research Personnel; Resources; Role; Shapes; Source; Sperm Head; Spermatids; Spermatogenesis; Spermiogenesis; Tail; Testis; United States National Institutes of Health; Weight; cell motility; in vivo; male; member; mouse model; mutant; sperm cell; success; tool

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Genetic mouse models provide valuable in vivo tools to study the regulation of mammalian reproduction. Approximately 99% of the roughly 40,000 genes within the two genomes are conserved between mice and humans and thus, genes important for regulation of spermatogenesis are likely conserved between the two species. C3Fe;B6-repro27 and C3Fe:B6-repro29 are genetic mouse models produced using the chemical mutagen ethylnitrosourea. The mutations are recessively inherited and male specific. Male repro27 homozygotes display defects during the first wave of meiosis leading to significant germ cell loss. Surviving germs cells show defects in spermiogenesis characterized by the delayed formation of elongated spermatids wtih abnormally shaped sperm heads and no tails. Mutant testes are very small, epididymal sperm concentration is very low with low motility and no success with in vitro fertilization. C3Fe;B6-repro29 mice share several of the male-specific spermatogenic defects found in repro27 mice. Our data suggests that the repro27 phenotype is caused by a point mutation in the Golga3 gene located on Chr5. Golga3 encodes a golgi autoantigen, a member of the golgin protein family. The GOLGA3 protein is important for the redistribution of the Golgi apparatus during mitosis, plays a role in apoptosis, and is required sperm development. The repro29 mutation maps to Chr 5; sperm have defective heads and tails, and very low IVF success. However, testes weights are normal and the defect appears to be post-meiotic. Research will focus on the following specific aims 1. morphological and histological characterize spermatogenesis in C3Fe;B6-repro29; 2. genetically map the repro29 mutation using meiotic recombinants to narrow the candidate gene region; and 3. DNA sequence candidate genes to identify the genetic defect in C3Fe:B6-repro29 mice. The identification of genes and elucidation of the pathways required for normal germ cell development will help unravel the causes of human infertility.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目及 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 遗传小鼠模型为研究哺乳动物繁殖调节提供了有价值的体内工具。这两个基因组中大约 40,000 个基因中的大约 99% 在小鼠和人类之间是保守的，因此，对于调节精子发生重要的基因可能在两个物种之间是保守的。 C3Fe;B6-repro27 和 C3Fe:B6-repro29 是使用化学诱变剂乙基亚硝基脲产生的遗传小鼠模型。这些突变是隐性遗传的并且是男性特异性的。雄性repro27纯合子在第一波减数分裂期间表现出缺陷，导致显着的生殖细胞损失。存活的生殖细胞表现出精子发生的缺陷，其特征是细长精子细胞的形成延迟，精子头部形状异常，没有尾部。突变的睾丸很小，附睾精子浓度很低，活动力低，体外受精不成功。 C3Fe;B6-repro29 小鼠具有在 repro27 小鼠中发现的几种雄性特异性生精缺陷。我们的数据表明repro27表型是由位于Chr5上的Golga3基因的点突变引起的。 Golga3 编码高尔基体自身抗原，高尔基体蛋白家族的成员。 GOLGA3 蛋白对于有丝分裂过程中高尔基体的重新分配非常重要，在细胞凋亡中发挥作用，并且是精子发育所必需的。 repro29 突变映射到 Chr 5；精子的头部和尾部有缺陷，体外受精的成功率非常低。然而，睾丸重量正常，缺陷似乎是减数分裂后的。研究将集中在以下具体目标 1. C3Fe;B6-repro29; 中精子发生的形态学和组织学特征。 2. 利用减数分裂重组体对repro29突变进行基因定位，缩小候选基因区域； 3. 用于鉴定 C3Fe:B6-repro29 小鼠遗传缺陷的 DNA 序列候选基因。 基因的鉴定和正常生殖细胞发育所需途径的阐明将有助于揭示人类不育的原因。