A Mouse Model for Complex Human Diseases

复杂人类疾病的小鼠模型

• 批准号: 7126581
• 负责人: JAMES M CHEVERUD
• 金额: $ 7.64万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-04-01 至 2006-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7126581
• 关键词: Mouse; Model; Complex; Human; Diseases

EXCEED THE SPACE PROVIDED. We propose to completethe developmentof a large series of recombinant inbred (RI) strains formed from the intercross of LG/J and SM/J mouse strains. These strains have already completed two-thirds of the generations needed to reach effective inbred status. We will also score a large number of polymorphic microsatellite markers in these strains to genetically characterize them for our own work and the work of others using the RI strain set. In additionto developing RI strains, we will maintain an advanced intercross (AI)strain. This strain was formed by random mating from the same F2 populationused in generating the RI strains. The combination of RI and AI strains from the same intercross will be a powerful resource for quantitative trait locus mapping for a wide variety of characters. We will test the RI strains for genetic variation in maternal effects on both neonatal and adult phenotypes using 40 reciprocal crosses between the RI strains and a standard inbred strain, C57BL/6J. In this design genetically different mothers give rise to genetically identical offspring so that reciprocal differences are due to genetic effects on the environment a mother provides for her offspring. In addition, we will test the "thrifty phenotype" hypothesis that states that pre- and neonatal environment affects risk for diseases (hypertension, diabetes, obesity, coronary artery disease, etc.) in adulthood. Poorly nourished neonates adapt to lownutrition levels in utero and soon after birth. This adaptation persists into adulthood so they are particularly susceptible to the deleterious effects of a high fat diet later in life. The offspring from the reciprocal crosses will receive either a high or a low fat diet after weaning. We will test whether animals subjected to relatively poor pre-and neonatal environments respond more strongly to the high fat diet. We will map quantitative trait loci for these genetic maternal effects and their interaction with diet. PERFORMANCE SITE ========================================Section End===========================================

超出所提供的空间。 我们建议完成LG/J和SM/J小鼠品系杂交形成的一系列重组近交系（RI）品系的开发。这些品系已经完成了达到有效近交状态所需的三分之二世代。我们还将在这些菌株中对大量的多态性微卫星标记进行评分，以便为我们自己的工作和其他使用RI菌株集的工作进行遗传表征。除了开发RI品系外，我们还将保持先进的互交（AI）品系。该菌株是由用于产生RI菌株的相同F2群体通过随机交配形成的。来自同一互交的RI和AI品系的组合将是一个强大的资源，为各种性状的数量性状基因座定位。 我们将测试RI菌株的遗传变异的母体对新生儿和成人表型的影响，使用40个RI菌株和一个标准的近交系，C57 BL/6 J之间的相互杂交。在这种设计中，基因不同的母亲会产生基因相同的后代，因此相互差异是由于母亲为后代提供的环境的遗传效应。此外，我们还将检验“节俭表型”假说，该假说指出，产前和新生儿环境影响疾病（高血压、糖尿病、肥胖、冠状动脉疾病等）的风险。在成年期。营养不良的新生儿在子宫内和出生后不久就适应了低营养水平。这种适应持续到成年，所以他们在以后的生活中特别容易受到高脂肪饮食的有害影响。从正反交的后代将接受高或低脂肪饮食断奶后。我们将测试是否动物受到相对较差的产前和新生儿环境更强烈地响应高脂肪饮食。我们将绘制这些遗传母体效应及其与饮食相互作用的数量性状基因座。性能现场=