IMMUNOGENETICS OF SPERMATOZOA, EGGS, AND EMBRYOS

精子、卵子和胚胎的免疫遗传学

• 批准号: 3311353
• 负责人: KAREN J ARTZT
• 金额: $ 19.08万
• 依托单位: UNIVERSITY OF TEXAS AT AUSTIN
• 依托单位国家: 美国
• 财政年份: 1976
• 资助国家: 美国
• 起止时间: 1976-05-01 至 1996-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3311353
• 关键词: cell differentiation; egg /ovum; embryo /fetus; genetic mapping; genetic recombination; genetic transcription; genetic translation; genetically modified animals; growth /development; histocompatibility antigens; immunochemistry; immunogenetics; laboratory mouse; laboratory rabbit; molecular cloning; protein structure function; sperm; cell differentiation; egg /ovum; embryo /fetus; genetic mapping; genetic recombination; genetic transcription; genetic translation; genetically modified animals; growth /development; histocompatibility antigens; immunochemistry; immunogenetics; laboratory mouse; laboratory rabbit; molecular cloning; protein structure function; sperm

The T/t complex on mouse chromosome 17 which includes the major histocompatibility complex (MHC), also contains a number of mutant gene that affect the differentiation of spermatozoa, and others that function during early embryonic development. Thus, it has been intensively investigated as model system for analyzing both immunobiology and differentiation, and their genetic control. Until recently, however, the molecular biology of the tau-complex was limited to chromosomal walking, marker identification, and random screening. This phase has now been accomplished. New results from this laboratory, obtained with a combination of genetic and molecular techniques have shown that the MHC has become the site major interest in the tau-complex and provided the tools to investigate a gene complex that regulates development in a mammal. Five out of six newly cloned male germ-cell-expressed genes residing in the MHC show expression changes in wild type versus tau-mutant testis. In terms of early embryo development, of the four recessive, early embryo tau-lethal genes interspersed with MHC genes , two have been more precisely located: tw5 is genetically inseparable from H-2K, and one of the earliest acting mammalian lethals, t12, is located either in the TL region or the uncloned "gap" between the TL and Qalpha regions. The early-embryo expressed transcription factor, Oct-4, has also been mapped to the gap between TL and Qalpha, and preliminary studies indicate it may well be t12. This project proposes three complementary strategies to define the molecular and biological function of these interesting tau-complex genes. (1) Analyze the cloned testis-expressed genes at the transcriptional, translational, and protein level. Ultimately, we will employ transgenic technology to study their dominant function. (2) Identify and map cloned genes, both from our laboratory and others, that are transcribed from within the tau-complex, and expressed in early mouse embryos. We will concentrate on those that are candidates for the tau-lethal mutation. Currently, this includes Oct-4 and six other early embryonic tau/tau complex encoded cDNAs. (3) Recombinational genetic analysis of the tau/tau complex region to support the molecular and functional analysis. Our long- term objective is to understand the molecular mechanisms and genetic control of cellular commitment.

小鼠染色体17上的T/T复合物，其中包括主要 组织相容性复合物（MHC）还包含许多突变基因 影响精子的差异化，以及其他功能 在早期胚胎发育期间。 因此，它一直是 被调查为分析免疫生物学和 分化及其遗传控制。 但是直到最近， tau复合物的分子生物学仅限于染色体行走， 标记识别和随机筛选。 这个阶段现在已经 成就。 该实验室的新结果，通过 遗传技术和分子技术的组合表明MHC已有 成为tau复合物的现场主要兴趣，并为 研究一种调节哺乳动物发育的基因复合物。 五 在MHC中的六个新克隆的雄性细菌表达的基因中 显示野生型与tau突变睾丸的表达变化。 按照 早期胚胎发育，四个隐性，早期的胚胎tau lethal 散布在MHC基因的基因中，两个基因更为精确： TW5在遗传上与H-2K是不可分割的，也是最早的表演之一 哺乳动物致命T12位于TL区域或未串联的哺乳动物 TL和Qalpha区域之间的“差距”。 早期的Embryo表示 转录因子10月4日也已映射到TL和TL之间的差距 Qalpha和初步研究表明它很可能是T12。 该项目提出了三种互补策略来定义 这些有趣的tau复合基因的分子和生物学功能。 （1）分析转录的克隆睾丸表达的基因， 翻译和蛋白质水平。 最终，我们将采用转基因 研究其主要功能的技术。 （2）识别和映射克隆 来自我们的实验室和其他人的基因都从 在tau复合物中，并在早期的小鼠胚胎中表达。 我们将 专注于那些是tau致命突变的候选者。 目前，其中包括10月4日和其他六个早期的胚胎tau/tau 复杂编码的cDNA。 （3）重组遗传分析 tau/tau复合区域以支持分子和功能分析。 我们的长期目标是了解分子机制和 细胞承诺的遗传控制。