Abstract
Introduction & background: nSMase2 is an enzyme converting sphingomyelin into ceramide. Others have proposed that nSMase2 activation and ceramide production are linked to emphysema development. The goal of this study was to test the effect of nSMase2 deficiency on lung phenotype in mice.
Animals: The mouse mutation fro carries a deletion within the nSMase2-encoding gene, rendering this enzyme inactive. In this study, we analyzed lung histology and lung function in adult fro mice.
Methods: Mean linear intercept (Lm) and alveolar destructive index (DI) were used to assess morphological changes in lungs. Lung compliance was measured to assess changes in lung function.
Results: We found that lungs of nSMase2-deficient mice exhibited emphysematous changes.
Both Lm and DI were significantly increased in fro/fro mice.
Consistent with emphysema, lung compliance was increased in fro/fro mice.
We found that heterozygous females were less affected than heterozygous males.
Conclusion: In contradiction with the current hypothesis, we have shown that nSMase2-deficient mice develop emphysema. We conclude that at least some levels of ceramide are necessary to ensure proper lung development.
- © 2011 ERS
