Quantitative expression analyses of candidates for alternative anion conductance in cystic fibrosis mouse models.
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.
Braun
Josephine
J
Department of Veterinary Pathology, Faculty of Veterinary Medicine, Freie Universität Berlin, Robert-von-Ostertag Straße 15, 14163 Berlin, Germany.
Mundhenk
Lars
L
Range
Friederike
F
Gruber
Achim D
AD
D000818:Animals; D018118:Chloride Channels / Q000235:genetics* / Q000378:metabolism*; D003199:Computer Systems; D003550:Cystic Fibrosis / Q000235:genetics* / Q000378:metabolism*; D004195:Disease Models, Animal; D015536:Down-Regulation; D005260:Female; D041981:Gastrointestinal Tract / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism; D007473:Ion Channels / Q000235:genetics*; D008565:Membrane Proteins / Q000235:genetics*; D051379:Mice; D010641:Phenotype; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism*; D014018:Tissue Distribution
D018118:Chloride Channels; C116464:Clca3a1 protein, mouse; D007473:Ion Channels; D008565:Membrane Proteins; D012333:RNA, Messenger; C555399:TTYH3 protein, mouse