Novel models for gastrointestinal disease, physiology and development

胃肠道疾病、生理学和发育的新模型

• 批准号: 7386962
• 负责人: Ian R van Driel
• 金额: $ 13.84万
• 依托单位: UNIVERSITY OF MELBOURNE
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-04-15 至 2010-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7386962
• 关键词: Address; Affect; Animal Model; Barrett Esophagus; Biological Process; Biology; Cancerous; Cells; Chemicals; Chromosome Mapping; Chronic; Colitis; Colon; Condition; Crohn' s disease; DNA; DNA Sequence; Defect; Development; Diarrhea; Disease; Disease model; Ethylnitrosourea; Etiology; Event; Exhibits; Gastritis; Gastrointestinal Diseases; Gastrointestinal tract structure; Gene Mutation; Genes; Genetic Variation; Genus Cola; Health; Histological Techniques; Human; Immune response; Inflammation; Inflammatory; Inflammatory Bowel Diseases; Inflammatory Response; Intestinal Cancer; Intestinal Metaplasia; Intestines; Knowledge; Laboratories; Lead; Lesion; Libraries; Malignant Neoplasms; Maps; Modeling; Molecular; Molecular Genetics; Molecular and Cellular Biology; Mucous Membrane; Mus; Mutagenesis; Mutant Strains Mice; Mutate; Mutation; Numbers; Outcome; Pathology; Pathway interactions; Personal Satisfaction; Phenotype; Physiology; Point Mutation; Positioning Attribute; Premalignant; Process; Rate; Resources; Screening procedure; Stomach; Stomach Carcinoma; Tissues; Ulcerative Colitis; Variant; Work; base; body system; cell type; disorder control; gastrointestinal; gastrointestinal epithelium; human disease; interest; malignant stomach neoplasm; mouse genome; mouse model; mutant; novel

DESCRIPTION (provided by applicant): The overall aims of this proposal are to produce and characterise new mutant mouse strains that will be applicable to the study of diseases and biology of the gut and allow the identification of genes involved in regulating these processes. Inflammatory diseases of the gut including ulcerative colitis, Crohn's disease and gastritis are the result of a destructive inflammatory response. Despite recent advances, the basis for these diseases remains unclear and we know little about the normal molecular mechanisms that control inflammation in the gut. The events that underlie the cell development in gut epithelia are poorly understood, as are the pathological outcomes of aberrant development that frequently develop into cancer. To identify new animal models that address these issues a screen of mice that have been mutated with a chemical has been initiated. This approach has been used very successfully to discover genes that control disease and development in other organ systems. The entire gut will be examined in these mutant mice to detect abnormalities that mimic human disease. Once located the positions and identities of the mutated genes will be determined. To our knowledge, no other laboratories in the world are screening for gut disease mutants in the manner described here, and therefore we have a strong competitive advantage in detecting and developing new mouse models of gut disease.Project Narrative Diseases of the gut including inflammatory bowel disease, bowel cancer and stomach cancer are major health problems affecting many millions of people world-wide. This project seeks to discover new models for these diseases and the pathological conditions that predispose to them, and which will facilitate a greater understanding of these conditions and the development of new treatments.

描述（由申请人提供）：本提案的总体目标是生产和表征新的突变小鼠菌株，这些菌株将适用于肠道疾病和生物学的研究，并允许识别参与调节这些过程的基因。包括溃疡性结肠炎、克罗恩病和胃炎在内的肠道炎症性疾病都是破坏性炎症反应的结果。尽管最近取得了进展，但这些疾病的基础仍不清楚，我们对控制肠道炎症的正常分子机制知之甚少。肠道上皮细胞发育背后的事件尚不清楚，就像异常发育经常发展成癌症的病理结果一样。为了确定能够解决这些问题的新动物模型，研究人员对一种化学物质发生突变的小鼠进行了筛选。这种方法已经非常成功地用于发现控制其他器官系统疾病和发育的基因。将对这些突变小鼠的整个肠道进行检查，以发现模仿人类疾病的异常情况。一旦定位，突变基因的位置和特性将被确定。据我们所知，世界上没有其他实验室以这里描述的方式筛选肠道疾病突变体，因此我们在检测和开发新的肠道疾病小鼠模型方面具有很强的竞争优势。项目的叙述