Mouse 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 cftrtm1Hgu mouse. Weight gain, body weight and life-span of cftrtm1Hgu mice were significantly reduced compared with control mice. cftrtm1Hgu 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 cftrtm1Hgu mice during their first year of life. The alveolar surfactant phospholipid pool was increased in cftrtm1Hgu mice by 1.5- to 2-fold compared with Ztm:MF1 controls. Alveolar clearance of γ-labelled scandium oxide – the first report of lung clearance measurement in living mice – was reduced in cftrtm1Hgu mice compared with littermate controls. Although no progressive lung pathology was seen in the cftr expression of cftrtm1Hgu mice, surfactant phospholipid homeostasis, and alveolar and mucociliary clearance were abnormal. Therefore, the described model is useful for studying the initial CF lung pathophysiology.

Keywords:
Alveolar clearance, CFTR, Cystic fibrosis, Lung pathology, Surfactant, Transgenic mouse disease model
This content is only available via PDF.
© 2002 S. Karger AG, Basel
2002
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.