GENE EXPRESSION PATTERNS DURING SPERMATOGENESIS

精子发生过程中的基因表达模式

• 批准号: 7720453
• 负责人: CAROL C LINDER
• 金额: $ 9.46万
• 依托单位: NEW MEXICO STATE UNIVERSITY LAS CRUCES
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-05-01 至 2009-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7720453
• 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.

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 小鼠遗传模型为研究哺乳动物生殖调控提供了有价值的活体工具。在这两个基因组中的大约40,000个基因中，大约99%在老鼠和人类之间保守，因此，对调节精子发生至关重要的基因可能在两个物种之间保守。C3Fe；B6-repro27和C3Fe：B6-repro29是使用化学诱变剂乙基亚硝脲产生的遗传小鼠模型。这些突变是隐性遗传的，是男性特有的。雄性REPRO27纯合子在第一波减数分裂中表现出缺陷，导致显著的生殖细胞损失。存活的生殖细胞在精子发生过程中表现出缺陷，其特征是细长精子细胞的形成延迟，精子头部形状异常，没有尾巴。突变的睾丸非常小，附睾精子密度很低，活动率很低，体外受精不成功。C3Fe；B6-repro29小鼠有几个在repro27小鼠中发现的男性特有的生精缺陷。我们的数据表明，repro27的表型是由位于chr5上的Golga3基因点突变引起的。Golga3编码一种高尔基自身抗原，是高尔基蛋白家族的成员。GOLGA3蛋白在有丝分裂过程中对高尔基体的重新分布很重要，在细胞凋亡中发挥作用，是精子发育所必需的。Repro29突变映射到Chr 5；精子头部和尾部有缺陷，试管受精成功率非常低。然而，睾丸重量是正常的，缺陷似乎是减数分裂后的。研究将集中于以下具体目标：1.C3Fe精子发生的形态和组织学特征；B6-repro29；2.利用减数分裂重组体缩小候选基因区域的遗传图谱；以及3.DNA序列候选基因以识别C3Fe：B6-repro29小鼠的遗传缺陷。鉴定基因和阐明正常生殖细胞发育所需的途径将有助于揭开人类不孕不育的原因。