INFLUENCE OF GENETIC BACKGROUND ON LIVER FLUX PROFILES IN MICE

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。我们目前对脂肪分布和体重调节的大部分知识都是基于对突变小鼠的研究。然而，矛盾的是，这些研究的最终目标人类疾病，如2型糖尿病和肥胖症，被认为是多个易感基因的微小贡献加上与环境的相互作用的结果。因此，背景基因型也可能对表型有重要影响，甚至在单基因性状上也是如此。事实上，不同背景下相同的ob或db突变会导致不同程度的肥胖、高血糖和高胰岛素血症。目前，出于实际原因，不同的小鼠品系被用于药理学和遗传学研究。例如，FVB背景通常用于制造转基因小鼠，ICR是用于毒理学研究的健壮小鼠，C57BL/6的基因组已经测序。我们正在开发(相对)高通量的筛选方法，以通过涉及糖异生的关键途径来量化通量之间的关系。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Most of our current knowledge of fat distribution and regulation of body weight is based on studies in mutant mice. Paradoxically, however, the human diseases that are the ultimate target of these studies, such as type 2 diabetes and obesity, are thought to be the consequence of small contributions from multiple susceptibility genes plus an interaction with the environment. Thus, the background genotype may also have an important impact on the phenotype, even in monogenic traits. Indeed, the identical ob or db mutations on different backgrounds cause different degrees of obesity, hyperglycemia and hyperinsulinemia. Currently, different mouse strains are used in pharmacology and genetic studies for practical reasons. For example, the FVB background is commonly used to make transgenic mice, the ICR is a robust mouse used in toxicology studies, and the genome of C57Bl/6 has been sequenced. We are developing (relatively) high throughput screening methods to quantify the relationships among fluxes through key pathways involved in gluconeogenes