Modification of the salivary secretion assay in F508del mice — The murine equivalent of the human sweat test

Abstract

In 2005 Best and Quinton established the salivary secretion assay in mice for the in vivo characterization of new drugs against cystic fibrosis (CF). However, limited data are available and the predictive value of this in vivo assay for treatment effects in CF patients is not fully understood. Therefore, we revisited the salivary secretion assay and systematically investigated the salivary secretion rates in different murine backgrounds and sexes, as well as in different CF mouse models. Moreover, we established quantification of salivary chloride content. We found a strain- and sex-dependency of salivary secretion rates and were able to confirm the decreased β-adrenergic salivary secretion response in CFTR knockout mice (CFTR(tm1Unc)) as well as in the F508del CFTR mice of different origins (CFTR(tm1Kth) and CFTR(tm1Eur)). In heterozygous Cftr+/- and Cftr+/F508del mice, the isoprenaline-stimulated salivary secretion rate and the Cl(-) content were intermediate between values measured in WT and CF mice, indicating that this assay is also able to detect CF carriership. Pilocarpine-induced abnormalities in saliva chloride content in CF mice resembled the changes observed in the human sweat test. Determination of murine salivary chloride content in combination with salivary secretion rate in CF mice may render the salivary secretion assay as a powerful tool for validation of new CF treatments.