Metabolic syndrome components in murine models

Abstract

Animal models have enriched understanding of the physiological basis of metabolic disorders and advanced identification of genetic risk factors underlying the metabolic syndrome (MetS). Murine models are especially appropriate for this type of research, and are an excellent resource not only for identifying candidate genomic regions, but also for illuminating the possible molecular mechanisms or pathways affected in individual components of MetS. In this review, we briefly discuss findings from mouse models of metabolic disorders, particularly in light of issues raised by the recent flood of human genome-wide association studies (GWAS) results. We describe how mouse models are revealing that genotype interacts with environment in important ways, indicating that the underlying genetics of MetS is highly context dependant. Further we show that epistasis, imprinting and maternal effects each contribute to the genetic architecture underlying variation in metabolic traits, and mouse models provide an opportunity to dissect these aspects of the genetic architecture that are difficult if not impossible to ascertain in humans. Finally we discuss how knowledge gained from mouse models can be used in conjunction with comparative genomic methods and bioinformatic resources to inform human MetS research.

Figure 1

Venn diagram illustrating the number of unique genes associated with a MetS component for humans, for mice, and their intersection

Figure 2

Genotypic means for a significant QTL for glucose tolerance in an F₁₆ LG/J and SM/J AIL (Wustl:LG,SM-G16). The QTL has significant additive effects in the full population, and significant additive and imprinting effects in males fed a high-fat diet. Note the scale is different in the high-fat fed males to accommodate that cohort’s higher mean values.