期刊
JOURNAL OF CYSTIC FIBROSIS
卷 12, 期 6, 页码 630-637出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.jcf.2013.05.001
关键词
Salivary secretion assay; Cystic fibrosis; Salivary chloride content; Human sweat test
资金
- EUROCARECF consortium activities of the 6th framework coordination action programme [LSHM-CT-2005-018932]
Background: 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. Methods: 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. Results: We found a strain- and sex-dependency of salivary secretion rates and were able to confirm the decreased beta-adrenergic salivary secretion response in CFTR knockout mice (CFTRtm1Unc) as well as in the F508del CFTR mice of different origins (CFTRtm1Kth and CFTRtm1Eur). 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. Conclusions: 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. (C) 2013 European Cystic Fibrosis Society. Published by Elsevier BAT. All rights reserved.
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