A dominant negative form of cJun affects genes that have opposing effects on lipid homeostasis in mice

cJun is a transcription factor activated by phosphorylation by SAPK/JNK MAP kinase pathway that has been linked to atherosclerosis. Adenovirus mediated gene transfer of a dominant negative form of cJun in C57BL/6 mice increased greatly the apolipoprotein E (ApoE) mRNA and plasma apoE levels and induced dyslipidmia, characterized by increased plasma cholesterol, triglyceride and VLDL levels and accumulation of discoidal HDL particles. Unexpectedly, infection of ApoE-/- mice with adenovirus expressing dn-cJun reduced by 50% plasma cholesterol, suggesting that the dn-cJun affected other genes that control plamsa cholesterol. To determine the molecular pathways implicated in this process we performed whole genome expression profiling using total RNA from the liver of infected ApoE-/- mice. Keywords: disease We extracted total RNA from 5 ApoE-/- mice infected with an adenovirus expressing dominant negative cJun and 5 ApoE-/- mice infected with a control adenovirus expressing GFP. Each RNA sample was hybridized to a different Affymetrix 430 2.0 array.