IMMUNOGENETICS OF SPERMATOZOA, EGGS, AND EMBRYOS

小鼠17号染色体上的T/t复合体，包括主要的 组织相容性复合体（MHC）中，也含有一些突变基因 影响精子分化的基因，以及其他 在早期胚胎发育过程中。 因此， 作为分析免疫生物学和 分化及其遗传控制。 然而，直到最近， tau复合物的分子生物学限于染色体步移， 标记鉴定和随机筛选。 这一阶段已经 完成了 从这个实验室获得的新结果， 遗传和分子技术的结合表明，MHC具有 成为该网站的主要兴趣在tau复杂，并提供了工具， 研究调节哺乳动物发育的基因复合体。 五 在六个新克隆的男性生殖细胞表达的基因中， 显示了野生型与tau突变睾丸中的表达变化。 方面 早期胚胎发育，四隐性，早期胚胎tau致死 基因散布在MHC基因中，有两个基因被更精确地定位： tw 5在遗传上与H-2K密不可分，也是最早起作用的病毒之一。 哺乳动物致死基因t12位于TL区或未克隆的 TL和Qalpha区域之间的“间隙”。 早期胚胎表达 转录因子Oct-4也被定位在TL和T2之间的差距上。 初步研究表明它很可能是t12。 该项目提出了三个互补战略，以确定 这些有趣的tau复合体基因的分子和生物学功能。 (1)对克隆的睾丸表达基因进行转录水平分析， 翻译和蛋白质水平。 最终，我们将采用转基因技术 技术来研究它们的主要功能。 (2)识别和映射克隆 基因，无论是从我们的实验室和其他人， 在tau复合物中，并在早期小鼠胚胎中表达。 我们将 集中在那些可能会导致tau致命突变的基因上 目前，这包括Oct-4和其他六个早期胚胎tau/tau 复杂编码的cDNA。 (3)遗传学分析 tau/tau复合物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， 细胞定型的遗传控制。

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.