Microarray expression profiling identifies genes with altered expression in HDL-deficient mice

Based on the assumption that severe alterations in the expression of genes known to be involved in high-density lipoprotein (HDL) metabolism may affec t the expression of other genes, we screened an array of >5000 mouse expres sed sequence tags For altered gene expression in the livers of two lines of mice with dramatic decreases in HDL plasma concentrations. Labeled cDNA fr om livers of apolipoprotein Al (apoAl)-knockout mice, scavenger receptor BI (SR-BI) transgenic mice, and control mice were cohybridized to microarrays . Two-sample t statistics were used to identify genes with altered expressi on levels in the knockout or transgenic mice compared with control mice. In the SR-BI group we found nine array elements representing at least Five ge nes that were significantly altered on the basis of an adjusted P value < 0 .05. In the apoAl-knockout group, eight array elements representing Four ge nes were altered compared with the control group (adjusted P < 0.05). Sever al of the genes identified in the SR-BI transgenic suggest altered sterol m etabolism and oxidative processes. These studies illustrate the use of mult iple-testing methods for the identification of genes with altered expressio n in replicated microarray experiments.