Genetic Modifiers of Diabetes

糖尿病的基因修饰

• 批准号: 8117790
• 负责人: STREAMSON C CHUA
• 金额: $ 34.2万
• 依托单位: ALBERT EINSTEIN COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-06-01 至 2013-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8117790
• 关键词: AP20187; Alleles; Apoptosis; Backcrossings; Base Pairing; Beta Cell; Biological Models; Candidate Disease Gene; Cell Death; Cell Proliferation; Chimeric Proteins; Chromosomes, Human, Pair 5; Chronic; Code; Complications of Diabetes Mellitus; Congenic Strain; Constitution; Data; Data Set; Diabetes Mellitus; Dimerization; Dose; Evaluation; FK506; FVB Mouse; Genes; Genetic; Genetic Models; Genetic Recombination; Genetic Variation; Genome; Genome Scan; Genotype; Hyperglycemia; Impact evaluation; Inbred Strain; Inbred Strains Mice; Injection of therapeutic agent; Insulin; Leptin; Leptin receptor mutation; Maps; Mediating; Modeling; Mouse Strains; Mus; Natural regeneration; Obese Mice; Obesity; Pancreas; Phenotype; Positioning Attribute; Predisposition; Process; Production; Rattus; Receptor Signaling; Recombinants; Recovery; Regulation; Resistance; Signal Transduction; Staging; Structure of beta Cell of islet; Syndrome; System; Tacrolimus Binding Proteins; Transgenes; Transgenic Mice; Variant; analog; congenic; db/db mouse; genetic selection; genetic variant; leptin receptor; mouse genome; mouse model; novel; promoter; recessive genetic trait; response; trait

DESCRIPTION (provided by applicant): This proposal aims to identify genetic variants that underlie susceptibility or resistance to developing diabetes and diabetic complications. We have developed a tractable genetic model system using inbred mouse strains carrying a mutation of the leptin receptor. The interaction between the obesity/diabetes syndrome caused by the leptin receptor deficiency and the specific genetic constitution of the inbred strain determines diabetes susceptibility or resistance. Genetic selection of specific chromosomal regions of the mouse genome has identified regions on mouse Chromosome 5 that is responsible for diabetes susceptibility. The region has been reduced to a 15 million base pair region containing ~200 identified genes. This proposal has three aims: 1. Define a critical interval of 100-300 kbp for Modb1. 2. Identify allelic variants that produce nonsynonymous coding sequence variants or expression differences between the C57BL/6 and FVB alleles. 3. Evaluate the impact of Modb1 alleles on beta cell regeneration/proliferation after induction of beta cell apoptosis.

描述（由申请人提供）：该提案旨在确定遗传变异的基础，这些变异是易感性或抗糖尿病和糖尿病并发症的抗性。我们已经使用携带瘦素受体突变的近交小鼠菌株开发了一种可探讨的遗传模型系统。由瘦素受体缺乏症引起的肥胖/糖尿病综合征与近交菌株的特定遗传构成之间的相互作用决定了糖尿病的易感性或抗性。小鼠基因组的特定染色体区域的遗传选择已经确定了导致糖尿病易感性的小鼠染色体上的区域。该区域已减少到1500万个碱基对区域，其中包含约200个鉴定的基因。 该提案有三个目标： 1。为MODB1定义100-300 kbp的关键间隔。 2。确定产生非同义编码序列变体或C57BL/6和FVB等位基因之间的表达差异的等位基因变体。 3。评估MODB1等位基因诱导β细胞凋亡后对β细胞再生/增殖的影响。