CONTROL OF ESTROGEN INDUCED PITUITARY HYPERPLASIA

老鼠将被用作一个模型系统来解决一个基本问题 的增长控制。 这里调查的具体情况是控制 垂体生长在雌激素的存在，并与 雌激素在肿瘤形成和生殖生物学中的作用。慢性 雌激素处理诱导大鼠垂体瘤 Fischer 344，而其他菌株，如Holtzman或Brown Norway， 抵抗这种诱导。先前的遗传分析表明， 效应是由于两个或三个遗传位点的变异。探讨 这种生长控制发生或不发生的机制， 负责的基因将被定位、克隆和分析。Fischer 344和 一种抗肿瘤的菌株，布朗挪威，将被杂交， 杂交以产生F2群体。将对F2代动物进行试验 垂体瘤的雌激素诱导和数量性状 雌激素诱导的肿瘤块将使用简单的重复序列作图 作为遗传标记和间隔作图程序MAPMAKER QTL。这 数据还将用于衡量每个映射的影响程度 基因座和等位基因之间的显性或加性关系， 每个轨迹相关基因将被分离出来进行测序 通过定位克隆进行分析。基因组消减杂交 被称为遗传定向表征差异技术 分析将被用来分离DNA序列多态性， 基因在定位的基因座上。这些多态性将被用作分子生物学。 标签来克隆参与诱导垂体瘤的实际基因。

The rat will be used as a model system to address a fundamental question of growth control. The particular case investigated here is control of pituitary growth in the presence of estrogen and is relevant to estrogen's role in tumor formation and reproductive biology. Chronic treatment with estrogen induces pituitary tumors in the rat strain Fischer 344 while other strains, such as Holtzman or Brown Norway, are resistant to this induction. Previous genetic analysis suggested that the effect is due to variation at two or three genetic loci. To investigate the mechanism by which this growth control occurs, or fails to occur, the genes responsible will be mapped, cloned, and analyzed. Fischer 344 and a tumor resistant strain, Brown Norway, will be crossed and their progeny intercrossed to produce an F2 population. The F2 animals will be tested for estrogen induction of pituitary tumors and the quantitative trait of estrogen-induced tumor mass will be mapped using simple sequence repeats as genetic markers and the interval mapping program MAPMAKER QTL. This data will also be used to measure the magnitude of effect of each mapped locus and the dominance or additivity relationship between alleles at each locus. The relevant genes will then be isolated for sequence analysis by positional cloning. The genomic subtractive hybridization technique known as genetically directed representational difference analysis will be employed to isolate DNA sequence polymorphisms in the genes at the mapped loci. These polymorphisms will be used as molecular tags to clone the actual genes involved in induction of pituitary tumor.