INFLUENCE OF GENETIC BACKGROUND ON LIVER FLUX PROFILES IN MICE

点击翻译按钮获取中文摘要

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