Gene expression profiling in the liver of 3-month old mice with a mutant Wrn protein compared to 3-month old WT mice. Mus musculus

Werner syndrome (WS) is a rare disorder characterized by the premature onset of a number of age-related diseases. The gene responsible for WS is believed to be involved in different aspects of transcription, replication, and/or DNA repair. We generated a mouse model with a deletion in the helicase domain of the murine WRN homologue that recapitulates most of the WS phenotypes including an abnormal hyaluronic acid excretion, higher reactive oxygen species (ROS) levels, increased genomic instability and cancer incidence resulting in a 10-15% decreased life span expectancy. In addition, WS patients and Wrn mutant mice show hallmarks of a metabolic syndrome including premature visceral obesity, hypertriglyceridemia, insulin-resistant diabetes type 2 and associated cardiovascular diseases. In this study, we compared the expression profile of liver tissues from 3-month old Wrn mutant mice 3-month old to wild type animals before the mutant animals exhibited any microscopic phenotype. Overall design: Microarray analyses were performed on the liver tissues of 3 months old mice. Four independent biological replicates of this experiment (wild type vs Wrn mutant mice) were carried out with a dye swap on two replicates of each genotype.