TERATOCARCINOMA AND EMBRYONAL TUMORS--SURFACE ANTIGENS

畸胎癌和胚胎肿瘤——表面抗原

• 批准号: 3165602
• 负责人: KAREN J ARTZT
• 金额: $ 30.9万
• 依托单位: UNIVERSITY OF TEXAS AT AUSTIN
• 依托单位国家: 美国
• 财政年份: 1987
• 资助国家: 美国
• 起止时间: 1987-01-01 至 1992-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3165602
• 关键词: biological polymorphism; cell differentiation; chromosome disorders; complementary DNA; developmental genetics; embryo /fetus antigen; embryo /fetus tissue /cell culture; embryo neoplasm; gel electrophoresis; gene expression; gene frequency; genetic library; genetic mapping; genetic regulation; genetically modified animals; glycoproteins; haploidy; histocompatibility gene; immune response genes; laboratory mouse; major histocompatibility complex; molecular cloning; molecular oncology; mutant; neoplasm /cancer genetics; nucleic acid sequence; plasmids; serology /serodiagnosis; surface antigens; teratoma; testis neoplasms; transcription factor; tumor antigens

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.

T/T/T-复合物在遗传控制中具有重要作用 正常早期发育中的细胞承诺。 一些 重要的新研究使隐性突变更多 分子分析可访问：（1）其中两个是 映射在良好的MHC中； 12在H-2D之间 TL和W5在遗传上与H-2K是不可分割的。 （2）185 kb -Haplotypes的H -2K区域已被克隆到宇宙中， 限制映射。 初步结果表明该区域 包含几个早期胚胎表达的序列。 （3） 与 - 相关细胞表面抗原GP87的结构基因具有 两个副本在物理上映射，一个在质量检查区域，一个 在两个H-2K基因之间。 我们打算使用这个最近的 尝试识别和结构表征的信息 有趣的早期胚胎表达基因，包括W5和12。 我们建议的总体方法是：1）搜索H-2K 使用来自胚胎的胚胎的区域cosmids使用来自 胚胎癌细胞，并使用来自 基因组宇宙探测可用的cDNA库的 正常的早期胚胎。 为了具体识别W5， 我们建议将其H-2K区域结构与 还原。 2）第二种方法是在结构上研究 -Haplotypes的D -TL区域的组织，其中12个基因 位于位置。 我们将使用厨师凝胶分析和现有 重组以完善图的地图位置12。3）最后，我们将 继续对相关糖蛋白的分子分析 抗原“糖蛋白87”通过检索和测序克隆 来自cDNA库。 我们将研究有趣的表达 使用各种技术（包括原位）识别的基因 杂交与切割胚胎的部分，在 突变体，转基因胚胎营救。 我们的长期目标是 了解分子机制和遗传控制 正常早期发展中的细胞承诺， 胚胎肿瘤中的非承诺。