PED GENE ACTION IN DEVELOPMENT AND REPRODUCTION

PED 基因在发育和繁殖中的作用

• 批准号: 6637957
• 负责人: CAROL M WARNER
• 金额: $ 28.53万
• 依托单位: NORTHEASTERN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-04-15 至 2006-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6637957
• 关键词: embryogenic cleavage; gene expression; genetically modified animals; laboratory mouse; major histocompatibility complex; mammalian embryology; mass spectrometry; protein structure function; yeast two hybrid system

DESCRIPTION: (Scanned from the applicant's description): The survival of preimplantation mammalian embryos, and the health of offspring arising from these embryos, is regulated by genes expressed during the preimplantation period of development. One example is the mouse Preimplantation embryo development (Ped) gene. The Ped gene has pleiotropic effects on the rate of embryonic cleavage division, survival to term, birth weight, and weaning weight. The Ped gene product has been identified as the major histocompatibility complex (MHC) encoded class lb protein Qa-2. Mouse embryos that express Qa-2 protein cleave at a faster rate, have a higher chance of survival to birth, and give rise to pups with higher birth and weaning weights than embryos that do not express Qa-2. The mystery is how the presence of a protein on the embryonic cell surface can signal the embryo to cleave at a faster rate than an embryo that is missing this protein. The finding that the Ped gene product is a MHC class Ib protein provides clues about what structural features to examine to solve this mystery. First, the nonameric peptides that bind to Qa-2 protein will be identified by using the technique of membrane preconcentration-capillary electrophoresis-tandem mass spectrometry (mPC-CE-MSfMS). Second, the types of accessory proteins that bind to Qa-2 protein to help mediate its function will be identified by using the yeast two-hybrid system. The important pleiotropic effects of the Ped gene on reproductive success make it desirable to search for a human homolog of this gene. The publication of the complete DNA sequence of the human MHC (HLA complex), along with recent literature on MHC class lb proteins encoded in the HLA complex, suggest that the most logical hypothesis is that a human homolog of Qa-2 is HLA-G. This hypothesis will be tested in the third specific aim by using an HLA-G transgenic mouse system.

描述：（从申请人的描述扫描）：生存的 植入前哺乳动物胚胎，和后代的健康所产生的 这些胚胎是由植入前表达的基因调控的， 发展时期。一个例子是小鼠植入前胚胎 发育（Ped）基因。Ped基因对细胞凋亡率具有多效性作用， 胚胎卵裂、足月存活率、出生体重和断奶 重量. Ped基因产物已被鉴定为主要的 组织相容性复合体（MHC）编码的Ib类蛋白Qa-2。小鼠胚胎 表达Qa-2蛋白以更快速率切割， 存活到出生，并产生具有更高出生和断奶体重的幼崽 不表达Qa-2的胚胎。神秘的是， 胚胎细胞表面的蛋白质可以发出信号，使胚胎在一个特定的时间分裂。 比缺少这种蛋白质的胚胎更快。的发现 Ped基因产物是一种MHC Ib类蛋白质，它提供了关于ped基因的结构 来解开这个谜团。首先，九聚体肽， 结合Qa-2蛋白将通过使用膜技术鉴定 预浓缩-毛细管电泳-串联质谱 （mPC-CE-MSfMS）。第二，与Qa-2结合的辅助蛋白的类型 蛋白质，以帮助调解其功能将确定通过使用酵母 双混合动力系统Ped基因在人乳腺癌中的重要多效性 繁殖成功使得寻找这种基因的人类同源物变得很有必要。 基因人类主要组织相容性复合体（HLA）DNA全序列的公布， 复合物），沿着最近的文献中编码的MHC Ib类蛋白质， HLA复合体，表明最合乎逻辑的假设是，人类同源物 Qa-2是HLA-G。这一假设将在第三个具体目标中得到检验， 使用HLA-G转基因小鼠系统。