GENE EXPRESSION PATTERNS DURING SPERMATOGENESIS

精子发生过程中的基因表达模式

• 批准号: 7960228
• 负责人: CAROL C LINDER
• 金额: $ 9.65万
• 依托单位: NEW MEXICO STATE UNIVERSITY LAS CRUCES
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-05-01 至 2010-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7960228
• 关键词: Apoptosis; Biomedical Research; Candidate Disease Gene; Cell Death; Computer Retrieval of Information on Scientific Projects Database; Defect; Development; Exhibits; Fertility; Fertilization; Funding; Gender; Gene Expression; Genes; Genetic; Germ Cells; Goals; Golgi Apparatus; Grant; Head; Human; Infertility; Institution; Male Infertility; Maps; Meiosis; Mus; Mutant Strains Mice; Mutation; New Mexico; Nonsense Codon; Pathway interactions; Pattern; Phenotype; Point Mutation; Proteins; Recombinants; Research; Research Personnel; Resources; Role; Signal Transduction; Source; Sperm Head; Spermatogenesis; Tail; Transcript; United States National Institutes of Health; egg; human male; male; member; mouse model; novel; prevent; protein transport; research study; sperm cell

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 overarching goal of this research is to identify genes and unravel novel mechanisms of gene expression responsible for male fertility. Two genetic mouse models, C3Fe;B6-repro27 (repro27) and C3Fe;B6-repro29 (repro29) are being used to accomplish this goal. Both strains exhibit defects in sperm development leading to gender-specific infertility. Mice with two copies of the repro27 mutation exhibit significant germ cell death during meiosis and defects in differentiation including sperm head and tail formation. We have identified a point mutation in the golgin subfamily A member 3 (Golga3) gene that inserts a premature stop codon into the transcript. Golga3 encodes a Golgi apparatus-associated protein involved in protein trafficking, apoptosis signaling, and spermatogenesis. The role of GOLGA3 in spermatogenesis is unknown. We are investigating mechanisms of GOLGA3 action in spermatogenesis by utilizing repro27 mutant mice. Defects in repro29 mice are evident in late spermatogenesis causing head and tail abnormalities that prevent fertilization of the egg. We are using meiotic recombinant mapping strategies to identify the gene responsible for the repro29 phenotype. We have narrowed the candidate gene region from 30 Mb to 1.57 Mb on Chr 5; this region contains 40 known genes currently being evaluated for differential sequence and gene expression patterns. Experiments using repro27 and repro29 mice will ultimately allow the identification of new genes and pathways that may be homologous in humans providing new clues and treatment options for human male infertility.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 这项研究的首要目标是确定基因，并解开负责男性生育力的基因表达的新机制。两种遗传小鼠模型C3 Fe;B6-repro 27（repro 27）和C3 Fe;B6-repro 29（repro 29）被用于实现这一目标。这两种菌株都表现出精子发育缺陷，导致性别特异性不育。 带有两个repro 27突变拷贝的小鼠在减数分裂过程中表现出显著的生殖细胞死亡和包括精子头部和尾部形成在内的分化缺陷。我们已经确定了一个点突变的Golgin亚家族A成员3（Golga 3）基因插入一个提前终止密码子到转录。Golga 3编码一种高尔基体相关蛋白，参与蛋白质运输、凋亡信号和精子发生。GOLGA 3在精子发生中的作用尚不清楚。我们正在研究GOLGA 3的作用机制，在精子发生利用rep 27突变小鼠。在生殖缺陷29小鼠是明显的，在后期精子发生导致头部和尾部异常，阻止卵子受精。 我们正在使用减数分裂重组定位策略，以确定基因的repro 29表型负责。我们已经缩小了候选基因区域从30 Mb到1.57 Mb的Chr 5，这个区域包含40个已知的基因，目前正在评估的差异序列和基因表达模式。使用repro 27和repro 29小鼠的实验最终将允许鉴定可能在人类中同源的新基因和途径，为人类男性不育提供新的线索和治疗方案。