Dextran sodium sulfate (DSS) is commonly used in mouse studies to induce a very reproducible\ncolitis that effectively mimics the clinical and histological features of human inflammatory bowel disease (IBD)\npatients, especially ulcerative colitis. However, the mechanisms of action of DSS remain poorly understood, and\nobservations by our laboratory and other groups indicate that DSS contamination of colonic tissues from DSStreated\nmice potently inhibits the quantitative reverse-transcription polymerase chain reaction (qRT-PCR)\namplification of mRNA.\u00a0A prior study used poly-A-mediated mRNA purification to remove DSS from RNA extracts, but we herein\nreport a second efficient and cost-effective approach to counteract this inhibition, using lithium chloride\nprecipitation to entirely remove DSS from RNAs. We also explored how DSS interferes with qRT-PCR process, and\nwe report for the first time that DSS can alter the binding of reverse transcriptase to previously primed RNA and\nspecifically inhibits the enzymatic activities of reverse transcriptase and Taq polymerase in vitro. This likely explains\nwhy DSS-treated colonic RNA is not suitable to qRT-PCR amplification without a previous purification step.\nIn summary, we provide a simple method to remove DSS from colonic RNAs, and we demonstrate for\nthe first time that DSS can inhibit the activities of both polymerase and reverse transcriptase. In order to reliably\nanalyze gene expression in the colonic mucosa of DSS-treated mice, the efficiency rate of qRT-PCR must be the\nsame between all the different experimental groups, including the water-treated control group, suggesting that\nwhatever the duration and the percentage of the DSS treatment, RNAs must be purified.