MOLECULAR CLONING OF THE MURINE LETHAL SPOTTING MUTATION

神经嵴由多能前体细胞组成， 胚胎的所有部分，并有助于发展广泛的阵列 细胞和组织。神经嵴细胞的脱落显示出多种多样的 由于其多样的细胞潜能，鼠致死 点样（LS）突变作为一个模型系统，以研究涉及的因素 在这些过程中，由于Is/ls小鼠在其末端缺乏肠神经节， 由于黑色素细胞的问题，它们的皮毛上有白色斑点。 这种小鼠还提供了先天性巨结肠的遗传模型， 缺乏神经嵴源性肠功能障碍 远端结肠的神经节基因的鉴定和分离 是我们理解基因突变的重要一步 其在神经嵴细胞迁移、分化、存活和/或 功能以及了解其在疾病过程中的作用。我们 已建立了一个高分辨率的分子遗传连锁图谱的IS 小鼠2号染色体上的区域，使用亚种间回交分析， 确定了Is突变的图谱位置，我们将染色体走到 物理克隆Is区域。我们将开发必要的资源， 识别和表征潜在的候选基因， 必须包含Is基因的定义区间。的组合 分子和遗传学的方法将提供基础 全面了解Is基因及其功能。这 研究将提供一个复杂的细胞相互作用的理解， 在发展过程中发生的，以及一个机会，调查 Is基因在肿瘤形成中的潜在作用。

The neural crest is composed of multipotent precursor cells which invade all parts of the embryo and contribute to the development of a wide array of cell and tissues. Abnormalities of neural crest cells display a variety of phenotypes due to their diverse cellular potentials. The murine lethal spotting (ls) mutation serves as a model system to study factors involved in these processes, since Is/ls mice lack enteric ganglia in their terminal bowel and have white spots on their coat due to problems with melanocytes. This mouse also provides a genetic model for Hirschsprung's disease, a human disorder in which there is a lack of neural crest derived enteric ganglia in the distal colon. Identification and isolation of the gene responsible for the Is mutation is an important step towards understanding its role in neural crest cell migration, differentiation, survival, and/or function as well as for understanding its role in the disease process. We have established a high resolution molecular genetic linkage map of the Is region on mouse chromosome 2 using intersubspecific backcross analyses and determined the map position of Is mutation, we will chromosome walk to and physically clone the Is region. We will develop resources necessary to identify and characterize potential candidate genes from the smallest defined interval that must contain the Is gene. The combination of molecular and genetic approaches to be taken will provide the foundation for a comprehensive understanding of the Is gene and its functions. This research will provide an understanding of the complex cellular interactions occurring during development as well as an opportunity to investigate the potential role of the Is gene in neoplasia.