The Hybrid Mouse Diversity Panel: a resource for systems genetics analyses of metabolic and cardiovascular traits

Abstract

The Hybrid Mouse Diversity Panel (HMDP) is a collection of approximately 100 well-characterized inbred strains of mice that can be used to analyze the genetic and environmental factors underlying complex traits. While not nearly as powerful for mapping genetic loci contributing to the traits as human genome-wide association studies, it has some important advantages. First, environmental factors can be controlled. Second, relevant tissues are accessible for global molecular phenotyping. Finally, because inbred strains are renewable, results from separate studies can be integrated. Thus far, the HMDP has been studied for traits relevant to obesity, diabetes, atherosclerosis, osteoporosis, heart failure, immune regulation, fatty liver disease, and host-gut microbiota interactions. High-throughput technologies have been used to examine the genomes, epigenomes, transcriptomes, proteomes, metabolomes, and microbiomes of the mice under various environmental conditions. All of the published data are available and can be readily used to formulate hypotheses about genes, pathways and interactions.

Genetic Regulation of Adipose Gene Expression and Cardio-Metabolic Traits

“…The HMDP has also helped researchers to understand contributions of genetic factors to cardio-metabolic traits. 72 The results of our cross-species analysis showed consistent association between traits and the expression of 25 genes in humans and mice, providing support for further study of these genes in mouse models ( Figure S5 and Table S13). Of course, the possibility exists that mechanisms might differ between species or that the wrong tissues are being compared.…”

“…72 In the panel, we identified microarray probes for 107 of the 140 mouse orthologs and tested them for association between adipose expression level and metabolic traits, including plasma lipids, insulin, glucose, and body-fat composition. We observed a significant correlation between 70 genes and one of the metabolic traits (p < 5.2 3 10 À5 ; 0.05/963 tests for nine traits 3 107 genes) ( Figure S5).…”

Genetic control of apoprotein A-I and atheroprotection: some insights from inbred strains of mice

“…The Hybrid Mouse Diversity Panel (HMDP) is made up of 30 classical inbred strains + 70 or more recombinant inbred strains derived from crosses between C57BL/6 and DBA mice (BxD RI) and C57BL/6 and A/J mice (BxA and AxB RI) [18]**. The use of this panel of mice allows for high-resolution gene mapping that can be correlated with metabolic phenotype analysis and global gene expression in various tissues.…”

The Metabolic Syndrome in Men study: a resource for studies of metabolic and cardiovascular diseases

“…It makes it possible to control environmental factors, guarantees the access for global molecular phenotyping, and makes it possible to integrate separate studies. All published data of the HMDP are available (92).…”

“…The HDMP is a collection of approximately 100 well-characterized inbred strains of mice that can be used to analyze the genetic and environmental factors underlying complex traits (92,93). There are several benefits of the HMDP.…”