PED GENE ACTION IN DEVELOPMENT AND REPRODUCTION

PED 基因在发育和繁殖中的作用

• 批准号: 6536170
• 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/6536170
• 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：（从申请人的描述中扫描）：生存 植入前哺乳动物胚胎及其后代的健康 这些胚胎受到植入前表达的基因的调节 发展期。小鼠植入前胚胎就是一个例子 发育（Ped）基因。 Ped 基因对发生率具有多效性作用 胚胎卵裂、足月存活、出生体重和断奶 重量。 Ped基因产物已被确定为主要的 组织相容性复合体（MHC）编码lb类蛋白Qa-2。小鼠胚胎 表达 Qa-2 蛋白裂解速度更快的细胞，有更高的机会 存活到出生，并产生具有更高出生体重和断奶体重的幼崽 与不表达 Qa-2 的胚胎相比。谜团是如何存在 胚胎细胞表面的蛋白质可以向胚胎发出信号，使其在某个时间裂解。 比缺少这种蛋白质的胚胎更快。研究结果表明 Ped 基因产物是 MHC Ib 类蛋白，提供了结构性线索 来检查这些特征以解开这个谜团。首先，非分子肽 与 Qa-2 蛋白的结合将通过使用膜技术来鉴定 预浓缩-毛细管电泳-串联质谱法 (mPC-CE-MSfMS)。二、与Qa-2结合的辅助蛋白类型 将使用酵母来鉴定有助于介导其功能的蛋白质 双混合系统。 Ped 基因的重要多效性作用 繁殖成功使得寻找该基因的人类同源物成为可取的 基因。人类 MHC（HLA）完整 DNA 序列的发表 复合体），以及最近关于MHC lb类蛋白编码的文献 HLA 复合体，表明最合乎逻辑的假设是人类同源物 Qa-2 的 是 HLA-G。该假设将在第三个具体目标中进行检验 使用 HLA-G 转基因小鼠系统。