Integration of QTL and bioinformatic tools to identify candidate genes for triglycerides in mice.

To identify genetic loci influencing lipid levels, we performed quantitative trait loci (QTL) analysis between inbred mouse strains MRL/MpJ and SM/J, measuring triglyceride levels at 8 weeks of age in F2 mice fed a chow diet. We identified one significant QTL on chromosome (Chr) 15 and three suggestive QTL on Chrs 2, 7, and 17. We also carried out microarray analysis on the livers of parental strains of 282 F2 mice and used these data to find cis-regulated expression QTL.

A Bayesian framework for inference of the genotype-phenotype map for segregating populations.

Complex genetic interactions lie at the foundation of many diseases. Understanding the nature of these interactions is critical to developing rational intervention strategies. In mammalian systems hypothesis testing in vivo is expensive, time consuming, and often restricted to a few physiological endpoints.

Uncovering genes and regulatory pathways related to urinary albumin excretion.

Identifying the genes underlying quantitative trait loci (QTL) for disease is difficult, mainly because of the low resolution of the approach and the complex genetics involved. However, recent advances in bioinformatics and the availability of genetic resources now make it possible to narrow the genetic intervals, test candidate genes, and define pathways affected by these QTL. In this study, we mapped three significant QTL and one suggestive QTL for an increased albumin-to-creatinine ratio on chromosomes (Chrs) 1, 4, 15, and 17, respectively, in a cross between the inbred MRL/MpJ and SM/J strains of mice.

Identification of genetic determinants of IGF-1 levels and longevity among mouse inbred strains.

The IGF-1 signaling pathway plays an important role in regulating longevity. To identify the genetic loci and genes that regulate plasma IGF-1 levels, we intercrossed MRL/MpJ and SM/J, inbred mouse strains that differ in IGF-1 levels. Quantitative trait loci (QTL) analysis of IGF-1 levels of these F2 mice detected four QTL on chromosomes (Chrs) 9 (48 Mb), 10 (86 Mb), 15 (18 Mb), and 17 (85 Mb).

High-fat diet leads to tissue-specific changes reflecting risk factors for diseases in DBA/2J mice.

The aim of this study was to characterize the responses of individual tissues to high-fat feeding as a function of mass, fat composition, and transcript abundance. We examined a panel of eight tissues [5 white adipose tissues (WAT), brown adipose tissue (BAT), liver, muscle] obtained from DBA/2J mice on either a standard breeding diet (SBD) or a high-fat diet (HFD). HFD led to weight gain, decreased insulin sensitivity, and tissue-specific responses, including inflammation, in these mice.