GTF2H2调控卵母细胞发育的分子机制研究

项目名称： GTF2H2调控卵母细胞发育的分子机制研究

项目编号： No.31471351

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 生物科学

项目作者： 苏友强

作者单位： 南京医科大学

项目金额： 85万元

中文摘要： 卵母细胞质量于生殖和后代健康的重要性已被广泛认识，然而哪些关键因子通过何种方式影响卵母细胞质量还很不清楚。我们的正向遗传学研究发现通用转录因子GTF IIH的p44亚基-GTF2H2特异影响卵母细胞质量。Gtf2h2基因突变雌鼠不育但雄性正常；其雌鼠虽能正常排卵且受精，但其受精卵很少能够正常卵裂并且很快死亡。GTF2H2 在卵母细胞内优势表达，并且与卵成熟中的纺锤体及微管组织中心共定位。鉴于GTF IIH在细胞转录起始、DNA损伤的核苷酸剪切修复、以及细胞周期调控中的重要功能，本项目将围绕该三个方面并以Gtf2h2基因突变和卵母细胞特异表达GTF2H2-3xDDK的转基因小鼠为模型，对GTF2H2调控卵母细胞发育进而影响卵母细胞发育潜能的作用和机制展开研究；以期解析Gtf2h2基因突变导致卵母细胞发育潜能低下的原因，并揭示卵母细胞内受GTF2H2调控并对卵母细胞质量起决定作用的关键基因。

中文关键词： 卵母细胞；发育潜能；基因组完整性；转录调控；减数分裂

英文摘要： Although it is well-appreciated that oocyte quality contributes significantly to the success of reproduction and the health of the offspring, little is known about what key factors by which means determine the developmental competence of the oocyte. Through a forward genetics screen, we have identified that the p44 subunit of general transcription factor IIF, GTF2H2, plays a pivotal role in the control of mouse oocyte development and thus affecting its quality. Gtf2h2 mutant females are infertile but the male is normal. Although the mutant can ovulate normally, and the ovulated oocytes are mature and can be fertilized in vitro, no cleavage occurs normally, and all the zygotes eventually die later during culture. GTF2H2 is robustly expressed by oocytes and co-localizes with meiotic spindles during maturation. Given that GTF IIH is essential for the control of transcriptional initiation, nucleotide excision repair of damaged DNAs, and cell cycle progression, we here plan to investigate how GTF2H2 control oocyte development and hence affecting its quality by focusing on these three aspects. The goal of this project proposal is to unravel the causes of diminished developmental competence in Gtf2h2-mutant oocytes, and reveal the key genes that are under the direct control by GTF2H2 and play key roles in determining oocyte developmental competence.

英文关键词： oocyte;developmental competence;genome integrety;transcriptional control;meiosis