A Mouse Model of Asthma
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
RespirologyVolume
19Editors
Bardin, PISSN
1323-7799Department/School
Tasmanian School of MedicinePublisher
Wiley-Blackwell Publishing AsiaPlace of publication
AustraliaEvent title
Thoracic Society of Australia & New Zealand and the Australian & New Zealand Society of Respiratory Science 2014 Annual Scientific MeetingsEvent Venue
Adelaide, AustraliaDate of Event (Start Date)
2014-04-04Date of Event (End Date)
2014-04-09Repository Status
- Restricted