GENETIC RESISTANCE TO MOUSE LUNG CARCINOGENESIS

小鼠肺癌的基因抗性

• 批准号: 6173933
• 负责人: YIAN WANG
• 金额: $ 30.13万
• 依托单位: OHIO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-09-04 至 2003-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6173933
• 关键词: artificial chromosomes; cancer risk; chemical carcinogenesis; gene deletion mutation; genetic library; genetic markers; genetic models; genetic polymorphism; genetic susceptibility; inbreeding; laboratory mouse; linkage mapping; lung neoplasms; model design /development; molecular cloning; neoplasm /cancer genetics; quantitative trait loci; sequence tagged sites

DESCRIPTION: The long-term goal of this proposal is to identify genes that are directly responsible for lung tumor resistance to chemical carcinogens. The specific aims are: 1) Fine mapping of QTLs from a 20-30 cM region to a 1-2 cM subregion of the chromosome, which will be accomplished by the following two complementary approaches. The first is to develop a series of congenic mice through repeated backcrossing with the parental strain carrying the resistance allele. The resulting congenic strain of mice will then be used to generate congenic mapping analysis of the chromosomal regions associated with the QTLs. The second is to conduct deletion mapping analysis of the chromosomal regions associated with the QTLs in mouse lung tumors derived from F1 hybrid mice, and to define a minimal region of chromosomal loss for each QTL. 2) Positional cloning of selected QTLs. A contig containing overlapping BAC/P1 clones for each fine mapped QTL (1-2 cM) will be constructed using closely linked polymorphic markers and genes. Candidate genes will be isolated by direct screening of cDNA libraries with the BAC/P1 clones. Candidate genes will be analyzed for sequence variations in the coding region and differences in RNA expression between parental alleles. 3) Functional characterizations will be conducted under this proposal to either confirm or eliminate candidate genes for mouse lung tumor resistance QTLs.

描述：该提议的长期目标是确定基因 直接负责肺肿瘤对化学致癌物的耐药性。 具体目的是：1）QTL从20-30 cm区域到A的精细映射 染色体的1-2厘米子区域，这将由 遵循两种互补方法。 首先是开发一系列 与父母菌株反复交叉的先天小鼠 携带阻力等位基因。 由小鼠产生的相对菌株将 然后用于生成染色体的先天映射分析 与QTL相关的区域。 第二个是进行删除映射 分析与小鼠肺中与QTL相关的染色体区域 源自F1杂种小鼠的肿瘤，并定义 每个QTL的染色体损失。 2）选定QTL的位置克隆。 一个 每个精细映射QTL包含重叠的BAC/P1克隆的重叠群（1-2 CM）将使用紧密连接的多态性标记和基因构建。 候选基因将通过直接筛选与 BAC/P1克隆。 将分析候选基因的序列变化 在编码区域和父母之间RNA表达的差异 等位基因。 3）将在此下进行功能表征 提议确认或消除小鼠肺肿瘤的候选基因 电阻QTL。