GENE EXPRESSION PATTERNS DURING SPERMATOGENESIS

精子发生过程中的基因表达模式

• 批准号: 7381753
• 负责人: CAROL C LINDER
• 金额: $ 5.3万
• 依托单位: NEW MEXICO STATE UNIVERSITY LAS CRUCES
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-07-01 至 2007-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7381753
• 关键词: GENE; EXPRESSION; PATTERNS; DURING; SPERMATOGENESIS

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. The goal of this project is to characterize repro27 mice, a model of male infertility. Preliminary data suggests that the repro27 phenotype is caused by a point mutation in the Golga3 gene. 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. Roughly 15% of couples in the US experience problems conceiving and about half are of male origin. It is hypothesized that genetic defects leading to abnormalities in sperm number, motility, and morphology may account for a significant percentage of idiopathic male infertility. 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. repro27 is a genetic mouse model produced using the chemical mutagen ethylnitrosourea. The mutation is recessively inherited and male specific. Male homozygotes have very low testis weight, very low epididymal sperm concentration, abnormally shaped sperm heads without tails, very low motility, and no success with in vitro fertilization. Sperm development is initially normal but testes begin to lose germ cells beginning just after 2 weeks of age. The specific aims of this research are to: (1) conduct a morphological and histological characterization; (2) characterize gene expression patterns to define the molecular defects; and (3) DNA sequence candidate genes. In summary, characterization of genetic models of male infertility increases our understanding of germ cell development. Identification of the mechanisms responsible for the novel repro27 mouse model will ultimately aid in deciphering the causes of male infertility in humans.

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。该项目的目标是描述雄性不育模型repro 27小鼠的特征。初步数据表明，repro 27表型是由Golga 3基因的点突变引起的。Golga 3编码高尔基体自身抗原，是高尔基体蛋白家族的一员。GOLGA 3蛋白对于有丝分裂期间高尔基体的重新分布很重要，在细胞凋亡中发挥作用，并且是精子发育所需的。在美国，大约有15%的夫妇遇到了怀孕问题，其中大约一半是男性。据推测，遗传缺陷导致精子数量，活力和形态异常可能占很大比例的特发性男性不育症。遗传小鼠模型为研究哺乳动物生殖调控提供了有价值的体内工具。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，对调节精子发生重要的基因可能在两个物种之间是保守的。Rep 27是使用化学诱变剂乙基亚硝基脲产生的遗传小鼠模型。该突变是重复遗传和男性特异性的。雄性纯合子具有非常低的睾丸重量、非常低的附睾精子浓度、异常形状的精子头部没有尾部、非常低的活动力和体外受精不成功。精子发育最初是正常的，但睾丸开始失去生殖细胞开始后2周龄。本研究的具体目的是：（1）进行形态学和组织学表征;（2）表征基因表达模式以确定分子缺陷;（3）DNA序列候选基因。总之，男性不育遗传模型的特征增加了我们对生殖细胞发育的理解。确定负责新的repro 27小鼠模型的机制将最终有助于破译人类男性不育的原因。