WILD-DERIVED GENETIC VARIATION

目的是识别和表征小鼠的遗传变异， 调节和结构基因座。 我们广泛地从各种各样的 通过从不同来源获得小鼠， 世界的地理区域。 从分类学上讲，这些老鼠包括 家鼠属物种在地理上是分开的，但很容易 与实验室老鼠杂交。 它还包括老鼠物种 困在东欧和西欧的野外栖息地，M. Horbulanus和 M spretus，在野外不杂交，但与 在动物群体条件下的实验室菌株。 我们还采集了老鼠的样本 在野外或地下不杂交的小鼠属的物种 实验室条件 这些资源目前维持在 在罗斯威尔公园繁殖殖民地，他们为我们提供了一个 基因结构和调控的大量遗传变异 这在实验室小鼠品系中不存在。 我们已经利用资源来确定基因表达的调控， 基因产物的合成和加工水平。 这项建议 描述了扩展这项工作的实验方法， 表征遗传变异的生物化学和分子基础， 葡萄糖醛酸苷酶在亚细胞定位中表达调节， 在睾丸激素处理的小鼠的肾脏中。 我们关心的是 表征参与基因调控的分子元件， 顺式 特别是，我们想知道， 包括β-葡萄糖醛酸苷酶、RP-2和Odk在内的神经调节基因， 在转录或RNA稳定化水平上顺式调节。 我们有 观察到小鼠种属之间在激素 小鼠肾脏中几个基因的调控。 我们提出了一些实验， 为了测试小鼠物种之间是否存在遗传变异， 作用调节元件，并且如果是，则表征 并将它们绘制在小鼠基因图谱上。 这一建议还将我们使用的化学和X射线诱变， 产生特定基因产物的突变。 实验方法是 详细鉴定X染色体上的突变以及常染色体 基因. X染色体突变将恢复X染色体疾病 在模拟人类医学关注的疾病的小鼠中。 了一种方法 提出用于测试X染色体基因的嵌合表达， 杂合子女性 它提供了一种简单、经济的测试， 使用X染色体上多达100个基因座的突变事件 单一生化测定。

The objective is to identify and characterize genetic variation in mice for regulatory and structural loci. We have drawn extensively from a diverse sampling of the mouse gene pool by obtaining mice from different geographical regions of the world. Taxonomically, these mice have included house mouse Mus species which are geographically separated but will readily interbreed with laboratory mice. It has also included mouse species trapped in field habitats in Eastern and Western Europe, M. Horbulanus and M spretus, which do not interbreed in the wild but do hybridize with laboratory strains in animal colony conditions. We have also sampled mouse species of the genus Mus which do not interbreed in the field or under laboratory conditions. These resources are currently maintained in breeding colonies at Roswell Park and they have supplied us with an extensive array of genetic variation for gene structure and regulation which is not present among the strains of laboratory mice. We have used resources to identify regulation of gene expression at the level of synthesis and processing of gene products. This proposal describes experimental approaches for extending that work and for characterizing the biochemical and molecular basis of genetic variation for the regulation of glucuronidase expression in subcellular localization and in the kidneys of testosterone treated mice. We are concerned with characterizing the molecular elements involved in gene regulation which act cis. In particular, we would like to known whether developmentally and hormonally regulated genes including, Beta-glucuronidase, RP-2 and Odk, are cis regulated at the level of transcription or RNA stabilization. We have observed substantial differences between Mus species in the hormonal regulation of several genes in mouse kidney. we have proposed experiments to test whether genetic variation is present among Mus species for trans acting regulatory elements and, if so, to characterize the expression of these genes and map them on the mouse gene map. This proposal also extends our use of chemical and X-ray mutagenesis to produce mutations in specific gene products. Experimental approaches are detailed to identify mutations on the X chromosome as well as for autosomal genes. X-chromosome mutations will be recovered for X-chromosome disorders in mice which model disorders of medical concern in humans. A method is proposed for testing mosaic expression of X-chromosome genes in heterozygous females. It provides a simple, economical test which can identify mutational events at up to 100 loci on the X chromosome using a single biochemical assay.