WILD DERIVED & INDUCED GENE VARIANTS AS MOUSE RESOURCES

目的是鉴定和表征小鼠的遗传变异。 监管和结构方面的定位。我们广泛地从不同的 从不同来源的小鼠获取小鼠基因库的抽样 世界各地的地理区域。从分类上讲，这些小鼠包括 不同地理位置的家鼠，但很容易 与实验室小鼠杂交。它还包括老鼠物种 被困在东欧和西欧的野外栖息地，大麦和 M spretus，它们不在野外杂交，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 不在田间或地下杂交的小鼠属的物种 实验室条件。这些资源目前维护在 罗斯威尔公园的繁殖地，他们为我们提供了 基因结构和调控的广泛遗传变异阵列 这在实验室小鼠的品系中是不存在的。 我们已经使用资源来确定基因表达的调控 基因产品的合成和加工水平。这项建议 描述扩展该工作的实验方法，并为 青枯菌遗传变异的生化和分子基础研究 葡萄糖醛酸苷酶在细胞内定位和表达的调节 在睾丸激素处理的小鼠的肾脏中。我们关心的是 描述参与基因调控的分子元件的特性 顺位。我们尤其想知道，在发展和发展方面， 激素调节基因，包括β-葡萄糖苷酸酶、RP-2和ODK，是 顺式转录因子在转录水平或RNA稳定水平上受到调节。我们有 观察到不同种小鼠在荷尔蒙上的显著差异 小鼠肾脏中几个基因的调控。我们已经提出了实验方案 测试转基因小鼠物种间是否存在遗传变异 作用调节元件，如果是，则表征其表达 并将它们映射到小鼠的基因图谱上。 这项提议还将我们使用化学和X射线诱变的范围扩大到 在特定基因产物中产生突变。实验方法是 详细识别X染色体上的突变以及常染色体 基因。X染色体突变将在X染色体疾病中恢复 在模拟人类医学疾病的小鼠中。一种方法是 建议用于检测X染色体基因的嵌合表达 杂合子的雌性。它提供了一种简单、经济的测试，可以 在X染色体上识别多达100个基因座的突变事件 单项生化检测。

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.