A Mouse Model for Complex Human Diseases

复杂人类疾病的小鼠模型

• 批准号: 6331724
• 负责人: JAMES M CHEVERUD
• 金额: $ 27.28万
• 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 2004-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6331724
• 关键词: behavioral genetics; coronary disorder; diabetes mellitus; disease /disorder model; ethology; genetic mapping; genetic polymorphism; hypertension; inbreeding; laboratory mouse; maternal behavior; obesity; quantitative trait loci

DESCRIPTION (Adapted from the applicant's abstract): We propose to complete the development of a large series of 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 addition to developing RI strains, we will maintain an AI strain. This strain was formed by random mating from the same F2 population used in generating the RI strains. The combination of RI and Al 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 low nutrition 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.

描述（改编自申请人摘要）：我们建议完成 发展了一个大系列的RI菌株形成的互交， LG/J和SM/J小鼠品系。 这些菌株已经完成了三分之二 达到有效的近亲繁殖状态所需的世代。 我们还将 在这些菌株中获得大量的多态性微卫星标记， 从基因上描述它们的特征，用于我们自己的工作和他人的工作， RI应变集。 除了开发RI菌株外，我们还将保持 AI菌株。 该品系是由同一F2随机交配而成 用于产生RI菌株的群体。 RI和Al的组合 来自同一杂交的菌株将是定量分析的有力资源。 对各种各样的性状进行性状基因定位。 我们将测试RI 母体对新生儿和成人的遗传变异 表型使用RI菌株和标准菌株之间的40个相互杂交 自交系C57 BL/6 J。 在这个设计中，基因不同的母亲 产生遗传上完全相同的后代， 母亲为后代提供的环境的遗传效应。 在 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的风险（高血压， 糖尿病、肥胖症、冠状动脉疾病等）在成年期。 差 有营养的新生儿在子宫内和产后不久适应低营养水平 出生 这种适应会持续到成年期， 在以后的生活中容易受到高脂肪饮食的有害影响。 的 从正反杂交的后代将得到高或低脂肪 断奶后的饮食 我们将测试动物是否受到相对较差的 产前和新生儿环境对高脂肪饮食的反应更强烈。 我们 将绘制这些遗传母体效应的数量性状基因座， 与饮食的互动。