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pubmed-article:12476034pubmed:abstractTextMouse models for cystic fibrosis (CF) mimic intestinal manifestations of the human disease, but the lung disease phenotypes are lacking in most strains. In this work, the issue was addressed whether aging of the respiratory tract leads to lung pathophysiology in the exon 10 insertional mutant cftr(tm1Hgu) mouse. Weight gain, body weight and life-span of cftr(tm1Hgu) mice were significantly reduced compared with control mice. cftr(tm1Hgu) mice expressed 20, 21 or 37% (median) of wild-type cystic fibrosis conductance transmembrane regulator (cftr) mRNA transcript in lungs, intestine and kidney. Wild-type cftr mRNA in renal and respiratory epithelia varied with age from levels similar to Ztm:MF1 controls at the age of 2 and 4 months to levels seen in patients with CFTR splice mutations beyond the age of 6 months. The morphology of the bronchi and more distal airways was apparently normal in cftr(tm1Hgu) mice during their first year of life. The alveolar surfactant phospholipid pool was increased in cftr(tm1Hgu) mice by 1.5- to 2-fold compared with Ztm:MF1 controls. Alveolar clearance of gamma-labelled scandium oxide - the first report of lung clearance measurement in living mice - was reduced in cftr(tm1Hgu) mice compared with littermate controls. Although no progressive lung pathology was seen in the cftr expression of cftr(tm1Hgu) mice, surfactant phospholipid homeostasis, and alveolar and mucociliary clearance were abnormal. Therefore, the described model is useful for studying the initial CF lung pathophysiology.lld:pubmed
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pubmed-article:12476034pubmed:copyrightInfoCopyright 2002 S. Karger AG, Basellld:pubmed
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pubmed-article:12476034pubmed:pagination89-97lld:pubmed
pubmed-article:12476034pubmed:dateRevised2006-11-15lld:pubmed
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pubmed-article:12476034pubmed:articleTitleResidual cftr expression varies with age in cftr(tm1Hgu) cystic fibrosis mice: impact on morphology and physiology.lld:pubmed
pubmed-article:12476034pubmed:affiliationFraunhofer Institute Toxicology and Aerosol Research, Medical School of Hannover, Hannover, Germany.lld:pubmed
pubmed-article:12476034pubmed:publicationTypeJournal Articlelld:pubmed
pubmed-article:12476034pubmed:publicationTypeComparative Studylld:pubmed
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