Novel CATERPILLER gene involved in mucosal inflammation

新型 CATERPILLER 基因参与粘膜炎症

• 批准号: 7109389
• 负责人: Beckley K Davis
• 金额: $ 5.04万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-07-01 至 2007-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7109389
• 关键词: biotechnology; cell type; colitis; cytogenetics; gastric mucosa; gene expression profiling; gene induction /repression; immune response; immunocytochemistry; immunoprecipitation; in situ hybridization; inflammatory bowel diseases; laboratory mouse; mass spectrometry; matrix assisted laser desorption ionization; microarray technology; molecular pathology; postdoctoral investigator; protein protein interaction; small interfering RNA; two dimensional gel electrophoresis

DESCRIPTION (provided by applicant): CATERPILLER proteins contain N-terminal effector domains, a nucleotide binding domain and a series of leucine rich repeats. These proteins are important in immune responses and disease associations have been linked to several, including MHCT2A, ClAS and NOD2/CARD15. Mutations in NOD2/CARD15 are associated exclusively with a subset of Crohn's disease patients. Crohn's disease and ulcerative colitis are complex and chronic disorders that are referred to as inflammatory bowel disease (IBD). Current dogma suggests that IBD results from aberrant immune responses to endemic microflora of the gut. We screened the expression profile of several novel CATERPILLER genes to determine if these genes were influenced in a mouse model for IBD. 16.1/NOD27 was shown to be upregulated ( approximately 100 fold) in the colon and cecum of ILl0-/-mice reared under SPF conditions relative to GF animals. Upregulation of 16.1/NOD27 correlated with spontaneous ex vivo IL-12 secretion of the transverse colon. Biochemical analysis of 16.1/NOD27 has shown it to be a regulator of NF-K B dependent gene expression. These data suggest a role for 16.1/NOD27 in the inflammatory response associated with active colitis.

描述（由申请人提供）：Caterpiller蛋白包含N末端效应域，核苷酸结合结构域和一系列富含亮氨酸的重复序列。这些蛋白质在免疫反应中很重要，疾病关联与包括MHCT2A，CLAS和NOD2/Card15在内的几种相关。 NOD2/Card15中的突变仅与克罗恩病患者的一部分有关。克罗恩病和溃疡性结肠炎是复杂的慢性疾病，被称为炎症性肠病（IBD）。当前的教条表明，IBD是由于对肠道特有微生物的异常免疫反应而引起的。我们筛选了几个新型毛毛虫基因的表达谱，以确定这些基因是否在IBD的小鼠模型中受到影响。 16.1/nod27显示在Ill0 - / - 小鼠的结肠和小鼠的结肠和盲肠中，相对于GF动物，在SPF条件下饲养。 16.1/nod27的上调与自发的离体离体IL-12分泌相关。 16.1/nod27的生化分析表明它是NF-K B依赖基因表达的调节剂。这些数据表明16.1/nod27在与活性结肠炎相关的炎症反应中起作用。