Quantitative expression analyses of candidates for alternative anion conductance in cystic fibrosis mouse models

BackgroundDiversity of cystic fibrosis (CF) phenotype in patients with the same CFTR-mutation raised the hypothesis that other factors modulate the phenotype including “alternative” calcium-activated anion currents (CaCC). This study compares the mRNA expression levels of candidate CaCC mediators in CF mouse models with wild type controls.MethodsmBEST1, mBEST2, mCLC-3B, mCLC-4, mTTYH3, mTMEM16A, mTMEM16F, mTMEM16K, mCLCA1 to -6 and SLC26A9 mRNA were quantified in CF-relevant tissues in cftrtm1Cam and cftrTgH(neoim)Hgu mice and controls using real-time RT-qPCR.ResultsNo consistent differences were observed except for mTTYH3 which was significantly down-regulated throughout the intestinal tract of cftrtm1Cam mice.ConclusionsDown-regulation of mTTYH3 may point towards its involvement in the complex CF pathology. However, the markedly reduced expression argues against a direct compensatory action as an alternative anion conductance. If any of the other candidates plays a role as modulator, factors other than transcriptional regulation and mRNA stability may be involved.