MODIFIERS OF INTESTINAL NEOPLASIA IN MICE

肠上皮是自我更新的。 这个组织是有丝分裂的 非常活跃，每天大约有1011次细胞分裂。 令人惊讶的是，大肠癌的发病率只急剧上升 在生命的第六个十年后，表明体内平衡必须是 由多个层次的监管来维持。 本条例 在患有常染色体显性遗传癌症的个体中， 家族性腺瘤性息肉病（FAP）。 这种综合征 其特征是形成大量结肠腺瘤， 进展为腺癌。 主要治疗是切除或切除 结肠切除术，然后进行放疗和/或化疗。 FAP的分子基础开始被理解。 其产生 大肠腺瘤性息肉病基因突变。实验室 博士W。F. Dove在小鼠的同源基因中发现了一个突变， 大肠腺瘤性息肉病基因ApcMin。 携带单一拷贝的小鼠 这种突变的发展多腺瘤整个肠道 道。 这项研究的目的是确定这种修饰语 表型。 一种方法是基于测试候选基因， 与人类结肠直肠癌有关 如果这些基因的等位基因 影响Min表型，那么这些等位基因和Min的组合 是人类疾病的更好模型， 基因和药物治疗的发展。 其他方法包括 设计用于鉴定Min表型的新修饰剂， 对通过杂交近交系分离的多态性修饰物作图，或 通过绘制遗传筛选中分离的突变修饰物。 等 修饰基因可能会为基因网络提供新的见解， 影响肠肿瘤形成。

The intestinal epithelium is self-renewing. This tissue is mitotically very active with approximately 1011 cell divisions per day. Surprisingly, the incidence rate of colorectal cancer only rises sharply after the sixth decade of life, indicating that homeostasis must be maintained by numerous layers of regulation. This regulation is breached in individuals afflicted with an autosomal dominant cancer syndrome called familial adenomatous polyposis (FAP). This syndrome is characterized by the formation of numerous colonic adenomas that can progress to adenocarcinomas. Primary treatment is resection or removal of the colon, followed by radiation and/or chemotherapy. The molecular basis of FAP is beginning to be understood. It arises from mutations in the adenomatous polyposis coli gene. The laboratory of Dr. W. F. Dove identified a mutation in the mouse homolog of adenomatous polyposis coli gene, ApcMin. Mice carrying a single copy of this mutation develop multiple adenomas throughout the intestinal tract. The goal of the proposed study is to identify modifiers of this phenotype. One approach is based on testing candidate genes that have been implicated in human colorectal cancer. If alleles of these genes affect the Min phenotype, then the combination of these alleles and Min is a better model of the human disease and should facilitate the development of gene and drug therapies. The other approaches are designed to identify novel modifiers of the Min phenotype either by mapping a polymorphic modifier isolated by crossing inbred strains or by mapping mutant modifiers isolated in a genetic screen. Such modifiers may provide new insights into the network of genes that can impact intestinal neoplasia.