MODIFIERS OF INTESTINAL NEOPLASIA IN MICE

肠道上皮是自我更新的。这个组织有丝分裂。 非常活跃，每天大约有1011个细胞分裂。 令人惊讶的是，结直肠癌的发病率只会急剧上升 在生命的第六个十年之后，表明动态平衡必须是 由多个层次的监管来维持。这项规定是 常染色体显性遗传性癌症患者发病 综合征称为家族性腺瘤性息肉病(FAP)。这种综合症是 特点是形成许多结肠腺瘤，可以 腺癌的进展。主要治疗方法是切除或切除 然后进行放射治疗和/或化疗。 人们开始了解FAP的分子基础。它出现了 来自结肠腺瘤性息肉病基因的突变。实验室 W.F.Dove博士在小鼠的同源物中发现了一种突变 腺瘤性息肉病结肠基因，ApcMin。携带单份拷贝的小鼠 这种突变的人会在整个肠道形成多发性腺瘤 一条小路。拟议的研究的目标是确定这一点的修饰语 表型。一种方法是基于测试具有 与人类结直肠癌有牵连。如果这些基因的等位基因 影响Min表型，然后这些等位基因与Min的结合 是人类疾病的一个更好的模型，应该有助于 基因和药物疗法的发展。其他方法包括 旨在通过以下方式识别Min表型的新修饰物 用近交系或杂交分离的多态修饰物作图 通过绘制分离在遗传屏幕上的突变修饰物。是这样的 修饰物可能提供对基因网络的新见解，这些基因网络可以 影响肠道肿瘤。

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.