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A Mouse Model of Asthma

conference contribution
posted on 2023-05-24, 13:14 authored by Wang, K, Le Crast, T, Larcombe, A, Graeme ZoskyGraeme Zosky, James, A, Noble, P

Introduction: Mouse models show that prolonged transforming growth factor alpha (TGFα) expression promotes chronic lung disease particularly in early growth response-1 (Egr-1) deficient mice. Notably, airway smooth muscle (ASM) is thickened and the exaggerated increase in lung resistance following bronchoconstrictor challenge supports a role in airway disease.

Aim: We aimed to determine the effect of short-term TGFα expression on ASM thickening and the development of airway hyperresponsiveness (AHR).

Method: TGFα was conditionally expressed in the airway epithelium of transgenic mice (Clara cell secretory protein-rtTA(+/−)/[tetO](7)-TGFα(+/−)) following 10 d exposure to doxycycline in chow. Egr-1 deficient mice on doxycycline (n = 5) were compared with a control group (n = 4) that were wild type for Egr-1 and did not receive doxycycline. Airway and lung mechanics were assessed by the forced oscillation technique and lungs fixed for subsequent airway morphometry.

Results: ASM thickening was detected in TGFα transgenic Egr-1 deficient mice (P < 0.05) following doxycycline treatment for 10 d. AHR was also demonstrated, defined by an exaggerated increase in Newtonian resistance after methacholine challenge (P < 0.05) compared with controls. In comparison, there was no effect on lung elastance or tissue damping before or after methacholine.

Conclusion: Doxycycline induced-TGFα expression in Egr-1 deficient mice, after 10 d, produces ASM remodelling and AHR with no change in parenchymal mechanics. Short-term TGFα expression in airway epithelial cells promotes features characteristic of asthma.

Funding

National Health & Medical Research Council

History

Publication title

Respirology

Volume

19

Editors

Bardin, P

ISSN

1323-7799

Department/School

Tasmanian School of Medicine

Publisher

Wiley-Blackwell Publishing Asia

Place of publication

Australia

Event title

Thoracic Society of Australia & New Zealand and the Australian & New Zealand Society of Respiratory Science 2014 Annual Scientific Meetings

Event Venue

Adelaide, Australia

Date of Event (Start Date)

2014-04-04

Date of Event (End Date)

2014-04-09

Repository Status

  • Restricted

Socio-economic Objectives

Clinical health not elsewhere classified

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    University Of Tasmania

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