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Updated: Jul 24, 2025
Automated Measurement of Pulmonary Emphysema and Small Airway Remodeling in Cigarette Smoke-exposed Mice
Published on: January 16, 2015
Characterization of a spontaneous mouse model of mild, accelerated aging via ECM degradation in emphysematous lungs
Ryosuke Tanino1, Yukari Tsubata2, Takamasa Hotta1
1Department of Internal Medicine, Division of Respiratory Medicine and Medical Oncology, Faculty of Medicine, Shimane University, 89-1 Enya, Izumo, Shimane, 693-8501, Japan.
Abstract:
Emphysema limits airflow and causes irreversible progression of chronic obstructive pulmonary disease (COPD). Strain differences must be considered when selecting mouse models of COPD, owing to disease complexity. We previously reported that a novel C57BL/6JJcl substrain, the Mayumi-Emphysema (ME) mouse, exhibits spontaneous emphysema; however, the other characteristics remain unknown. We aimed to characterize the lungs of ME mice and determine their experimental availability as a model. ME mice had a lower body weight than the control C57BL/6JJcl mice, with a median survival time of ~80 weeks. ME mice developed diffused emphysema with respiratory dysfunction from 8 to 26 weeks of age, but did not develop bronchial wall thickening. Proteomic analyses revealed five extracellular matrix-related clusters in downregulated lung proteins in ME mice. Moreover, EFEMP2/fibulin-4, an essential extracellular matrix protein, was the most downregulated protein in the lungs of ME mice. Murine and human EFEMP2 were detected in the pulmonary artery. Furthermore, patients with mild COPD showed decreased EFEMP2 levels in the pulmonary artery when compared to those without COPD. The ME mouse is a model of mild, accelerated aging with low-inflammatory emphysema and respiratory dysfunction that progresses with age and pulmonary EFEMP2 decrease, similar to that observed in patients with mild COPD.
Insights
The Mayumi-Emphysema mouse model exhibits spontaneous emphysema and respiratory dysfunction, mirroring mild chronic obstructive pulmonary disease (COPD) progression and decreased EFEMP2 levels in aging lungs.
Area of Science:
- Pulmonary Medicine
- Animal Models of Disease
- Proteomics
Background:
- Emphysema, a component of chronic obstructive pulmonary disease (COPD), causes irreversible airflow limitation.
- Selecting appropriate mouse models is crucial for studying complex diseases like COPD.
- A novel C57BL/6JJcl substrain, the Mayumi-Emphysema (ME) mouse, was previously identified to have spontaneous emphysema.
Purpose of the Study:
- To comprehensively characterize the lung phenotype of ME mice.
- To evaluate the suitability of ME mice as an experimental model for emphysema and COPD research.
Main Methods:
- Comparative analysis of ME mice and control C57BL/6JJcl mice.
- Assessment of respiratory function and lung histology.
- Proteomic analysis of lung tissue.
- Detection of EFEMP2 in murine and human pulmonary arteries.
- Comparison of EFEMP2 levels in mild COPD patients versus controls.
Main Results:
- ME mice exhibited lower body weight and a median survival of ~80 weeks.
- Progressive, diffused emphysema and respiratory dysfunction were observed in ME mice from 8 to 26 weeks of age, without bronchial wall thickening.
- Proteomic analysis identified downregulated extracellular matrix proteins, notably EFEMP2/fibulin-4.
- EFEMP2 levels were decreased in the pulmonary artery of mild COPD patients compared to controls.
Conclusions:
- The ME mouse serves as a valuable model for studying mild, accelerated aging-associated emphysema with low-inflammatory characteristics and age-related respiratory dysfunction.
- The model recapitulates the pulmonary EFEMP2 decrease observed in patients with mild COPD, highlighting its translational potential.
