The physiological consequences of this deficiency also need to be further examined in these models, and most importantly re-examined in patients. The near doubling of life expectancy for CF patients since the eighties has been a result of gradually improving the intensive clinical monitoring and treatment of the patients, rather than spectacular breakthroughs in fundamental science. intensive research marketing campaign in the past two decades, no magic bullet type of remedy for this devastating disease has been found. One of T56-LIMKi the problems facing the CF researcher offers been to generate models that emulate the complexities of the different cells affected by CF pathology. Cell T56-LIMKi tradition and mouse models have been very instructive but do possess severe limitations. Recently, the development of CFTR-deficient pigs (Rogerset al.2008;Stoltzet al.2010) and ferrets (Sunet al.2010) from the teams of Michael Welsh and John Engelhardt of Iowa university have provided new and exciting options. In this problem ofExperimental Physiology,Hui Liet al. (2010)seize this opportunity to study the thyroid gland in the CF SLC2A2 pig model, a somewhat neglected but potentially important cells in CF pathology. The authors show that cultured thyroid epithelium fromCFTR-knockout pigs lacks the signature short-circuit current response to the cAMP agonist isoprenaline. This is evidence that CFTR is definitely active like a controlled apical chloride conductance with this cells. Furthermore, they display the amiloride-sensitive sodium current, most probably carried by apicalENaCtype sodium ion channels, is enhanced in mutant epithelium compared with control epithelium, as with CF airways. In addition, they present a model in which the secretion of iodide ions through the ClIexchange carrier SLC26A4 depends on CFTR activity. This would clarify the subclinically reduced thyroid function reported in CF individuals, which in part relies of the availability of iodide in the thyroid follicles for the production of thyroid hormone. This study confirms the power of the CF pig model and opens fresh ways to study thyroid function. Like all seminal papers, it raises questions as well. The hypothetical CFTR-dependent iodide fluxes have not been measured directly in this system yet. This will further substantiate the claim. Furthermore, reduced production of thyroid hormone, subclinically or otherwise, is not yet founded in the pig model. Previously, inside a paper duly cited from the authors,Devuystet al.(1997)reported expression of CFTR mRNA and antigen in normal human being thyroid epithelial cells, and also observed a correlation between the quantity of epithelial cells positive for CFTR antigen and follicle size. However, the study byHui Liet al. (2010)does not indicate a difference in follicle size between normal and CFTR-deficient pigs. Furthermore, CFTR immunohistochemistry showing the cellular and subcellular localization of CFTR in pig thyroid gland is not offered yet. The CFTR-deficient pig model presents an ideal opportunity to do such studies and settle longstanding issues about the quality and specificity of CFTR antibody staining in cells expressing low levels of CFTR. The vast majority of CF patients produce a mutant form of CFTR with more or less residual activity, making a true bad control impossible. Another issue is the analysis of thyroid function in T56-LIMKi the different mutant CFTR mouse models and in the recently developed ferret model. This would establish whether the observed CFTR-related thyroid epithelial transport deficiency is definitely a cross-species trend in mutant animals. The physiological effects of this deficiency also need to be further examined in these models, and most importantly re-examined in patients. The near doubling of life expectancy for CF patients since the eighties has been a result of gradually improving the intensive clinical surveillance and treatment of the patients, rather than spectacular breakthroughs in basic science. However, studies in relevant cellular and animal model systems T56-LIMKi did contribute significantly by generating new insights, and provided testing grounds for novel concepts and therapeutics. In fact, the current pipeline is filled with promising candidates, T56-LIMKi ranging from anti-inflammatory brokers to compounds correcting mutant CFTR dysfunction. The focus on progressive CF airway disease is certainly justified in view of its relative contribution to the burden of CF pathology. However, recent studies, including the one discussed here, have shown that other tissues and cell types also deserve attention. Bile duct, gall bladder, kidney and salivary glands show CFTR-dependent function as well. Non-epithelial cell types, including easy muscle cells, bone- and cartilage-forming cells and cells of the immune system, express CFTR, and are likely to contribute to CF pathology in a.