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Published on: July 4, 2018
Quantitative expression analyses of candidates for alternative anion conductance in cystic fibrosis mouse models
Josephine Braun1, Lars Mundhenk, Friederike Range
1Department of Veterinary Pathology, Faculty of Veterinary Medicine, Freie Universität Berlin, Robert-von-Ostertag Straße 15, 14163 Berlin, Germany.
Background:
Diversity 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.
Methods:
mBEST1, mBEST2, mCLC-3B, mCLC-4, mTTYH3, mTMEM16A, mTMEM16F, mTMEM16K, mCLCA1 to -6 and SLC26A9 mRNA were quantified in CF-relevant tissues in cftr(tm1Cam) and cftr(TgH(neoim)Hgu) mice and controls using real-time RT-qPCR.
Results:
No consistent differences were observed except for mTTYH3 which was significantly down-regulated throughout the intestinal tract of cftr(tm1Cam) mice.
Conclusions:
Down-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.
