The Pirc Rat, a Newly Generated Model for Familial Human Colon Cancer

Pirc 大鼠，一种新生成的家族性人类结肠癌模型

基本信息

批准号：
7318692
负责人：
WILLIAM Franklin DOVE
金额：
$ 27.93万
依托单位：
UNIVERSITY OF WISCONSIN-MADISON
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-07-16 至 2012-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7318692
关键词：
Abbreviations Address Adenocarcinoma Adenomatous Polyposis Coli Age-Months Alleles Amber Azoxymethane Chemopreventive Agent Classification Colon Colon Carcinoma Colonic Polyps Colonoscopy Colorectal Cancer Drug Kinetics Endoscopy Ethylnitrosourea Fluorouracil Genes Genetic Genetic Predisposition to Disease Genetic Recombination Genomic Instability Genus Cola Goals Heterozygote Human Image Intestinal Neoplasms Intestines Invasive Karyotype Laboratory Rat Longevity Longitudinal Studies Loss of Heterozygosity Mammals Modeling Mus Mutagenesis Mutation Names Neoplasm Metastasis Neoplasms Nitrosourea Compounds Patients Pattern Phenotype Pongidae Positioning Attribute Rate Rattus Recombinants Research Resistance Screening procedure Single Nucleotide Polymorphism Small Intestines Staging Terminator Codon Testing Therapeutic adenoma celecoxib chemical carcinogen cohort in vivo kindred mouse model mutant mutation carrier polyposis rat genome tumor

项目摘要

DESCRIPTION (provided by applicant): END mutagenesis of the rat germline followed by screening for nonsense alleles in the Adenomatous polyposis coli (Ape) gene has generated inbred Fischer344 kindred carrying an X\pcam1137 nonsense allele. Heterozygotes for this mutation develop multiple colonic polyps within 3 months of age; the ratio of colonic polyps to neoplasms in the small intestine is far higher than that observed in mouse models of human colorectal cancer. For this reason, the kindred is designated F344-Pirc (polyposis in the rat colon). Research is proposed to address the following issues: To investigate the importance of conservative somatic recombination in the initiation of the familial adenoma and microadenoma To identify dominant resistance and susceptibility genetic modifiers of the Pirc phenotype in the rat genome To investigate invasive and metastatic stages of colon cancer that may be permitted by the longevity we observe in the initial cohort of Pirc rats To develop imaging of the Pirc rat in vivo by microCT, microPET and endoscopy, establishing the potential to perform longitudinal studies of chemopreventive and therapeutic treatment, using celecoxib and 5-FU as test cases

描述（由申请人提供）：大鼠种系的最终诱变，然后筛选腺瘤性息肉病（APE）基因中的无义等位基因，产生了携带X \ pcam1137废话等位基因的近杂交Fischer344。该突变的杂合子在3个月大的时间内发展出多个结肠息肉。小肠中结肠息肉与肿瘤的比率远高于在人类结肠癌的小鼠模型中观察到的。因此，该亲属被指定为F344-PIRC（大鼠结肠中的息肉病）。提出了研究以解决以下问题：研究保守性体细胞重组在开始的家族腺瘤和MICOXENAMA启动中的重要性，以鉴定大鼠基因组中PIRC表型的显性抗药性和易感性遗传修饰剂，以研究研究结肠的侵入性和转移阶段我们在PIRC大鼠初始人群中观察到的寿命可以允许的癌症，以通过MicroCT，MicroPET和内窥镜检查体内对PIRC大鼠的成像，从而有可能对化学预防和治疗治疗进行纵向研究，并使用Celecoxib和5 -fu作为测试用例