TERATOCARCINOMA AND EMBRYONAL TUMORS: SURFACE ANTIGENS

T/T复合体在遗传控制中起着重要作用。 正常早期发育中的细胞承诺。几个 重要的新研究使隐性致死突变 可用于分子分析：(1)其中两个已被 在特征良好的MHC中定位；12在H-2D之间 和t1，w5在遗传上与H-2K密不可分。(2)185KB 单倍型的H-2K区已在宇宙体和 限制已映射。初步结果表明这一区域 包含几个早期胚胎表达的序列。(3) A相关细胞表面抗原的结构基因gp87具有 物理映射的两个副本，一个在QA区域，一个在QA区域 在两个H-2K基因之间。我们打算利用最近的这一次 试图识别和描述结构特征的信息 有趣的早期胚胎表达基因包括w5和12。 我们提出的总体方法是：1)搜索H-2K 利用天冬氨酸脱氢酶基因构建胚胎表达基因的区域粘粒 胚胎癌细胞，并使用来自 探索可利用的cdna文库的基因组宇宙 正常的早期胚胎。为了特别识别W5， 我们建议将它的H-2K区结构与a 恢复原状。2)第二种方法是从结构上研究 12基因单倍型D-TL区的组织 已经找到了。我们将使用厨师凝胶分析和现有的 重组人来细化地图的位置12.3)最后，我们会 继续相关糖蛋白的分子分析 抗原“糖蛋白87”克隆的检索和测序 从c DNA文库中获得。我们将研究兴趣的表达 使用包括原位在内的各种技术鉴定基因 对胚胎切片进行杂交，在这种情况下 变种人，转基因胚胎拯救。我们的长期目标是 了解致病的分子机制和遗传控制 正常早期发育中的细胞承诺，以及 胚胎肿瘤中的不承诺。

The T/t-complex has an important role in the genetic control of cellular commitment in normal early development. Several important new studies make the recessive -lethal mutations more accessible to molecular analysis: (1) two of them have been mapped within the well characterized MHC; 12 is between H-2D and TL, and w5 is genetically inseparable from H-2K. (2) 185 kb of the H-2K region of -haplotypes has been cloned in cosmids and restriction mapped. Preliminary results indicate this region contains several early embryo-expressed sequences. (3) the structural gene for a -associated cell surface antigen, gp87, has two copies physically mapped, one in the Qa region and one between the two H-2K genes. We intend to use this recent information to try to identify and structurally characterize interesting early embryo-expressed genes including w5 and 12. The overall approaches we propose are: 1) to search the H-2K region cosmids for embryo expressed genes using cDNA from embryonal carcinoma cells, and to use unique copy probes from the genomic cosmids to probe available cDNA libraries from normal early embryos. In an effort to specifically identify w5, we propose to compare its H-2K region structure to that of a revertent. 2) The second approach is to structurally study the organization of the D-TL region of -haplotypes where the 12 gene is located. We will use CHEF gel analysis and existing recombinants to refine the map position of 12. 3) Finally, we will continue the molecular analysis of the -associated glycoprotein antigen "glycoproteins 87" by retrieving and sequencing clones from cDNA libraries. We will study the expression of interesting genes identified using a variety of techniques including in situ hybridization to cut sections of embryos and in the case of the mutants, transgenic embryo rescue. Our long term objective is to understand the molecular mechanisms and genetic control of cellular commitment in normal early development, and noncommitment in embryonal tumors.