We developed a low density Sterolgene v0 cDNA microarray for studies of cholesterol homeostasis and drug metabolism. We analyzed mouse liver samples from perturbation studies of cholesterol homeostasis and drug metabolism by diet, drugs and inflammation. The performance of the Sterolgene v0 was compared to the two commercial high density microarray platforms Agilent and Affymetrix. We hybridized the same RNA samples to the commercial platforms and show that the Sterolgene microarray performance is comparable in terms of detection of changes in cholesterol homeostasis and drug metabolism.
We show for the first time that isoforms of the cAMP response element modulator Crem regulate the circadian expression of Cyp51 and other cholesterogenic genes . In wild type mice the expression of Cyp51, Hmgs, Fpps, and Sqs is minimal between CT12-CT16 and peaks between CT20–CT24. Cyp51, Fpps and Sqs lost the circadian behavior while Hmgcr is phase advanced from CT20 to CT12. This coincides with a phase advance of lathosterol/cholesterol, as detected by GC-MS. Overexpression of CREM? and ICER has little effect on the Hmgcr proximal promoter but influence expression from the CYP51 promoter.