Studies on lung mechanics and morphometry in inbred mice

Mouse studies have yielded important information on the structure and functional development of biological systems. A communication by Tankersley, et al. showing that the C3H/HeJ (C3) strain had a total lung capacity 50% larger than the C57BL/6J (B6) strain (172) was the inspiration for these studies.;First, using quantitative morphometric analysis of airspace chord lengths (Lma) we assessed whether the relative size or numbers of alveoli in the C3, B6, and A/J strains are correlated with lung volume differences. Lma were significantly different among the 3 strains providing clear evidence of significant genetic differences in lung structure among mouse strains.;Although much of lung development occurs postnatally in rodents, it is uncertain at what age the differences between these strains become manifest. In the second study we performed quasi-static pressure-volume (P-V) curves and morphometric analysis on neonatal mice. The lung volume of C3 mice was substantially greater than B6 mice at all ages. In contrast, there was no difference in Lma of 3-day-old mice. With increasing age there was a progressive decrease in the Lma of both strains, the magnitude of the decrease in B6 Lma mice exceeding that of C3. The combination of parenchymal architectural similarity with lung air volume differences, and different rates of alveolar septation suggest that lung volume and alveolar dimensions are independently regulated.;In the previous studies, the "double-humped" P-V inflation curves of the mouse lung were observed. In the third study we examined P-V relations and Lma in the same three strains at multiple inflation pressures. P-V curves were recorded in situ with increasing peak inflation pressure up to 90 cmH2O. Lungs were quickly frozen at specific pressures for morphometric analysis. Inflation limbs never showed the appearance of a plateau with lung volume increasing 40-60% at pressures above 30 cmH 2O. In contrast parallel flat deflation limbs were always observed regardless of inflation pressure. Alveolar size increased monotonically with increasing pressure in all strains. These results suggest that the mouse lung never reaches a maximal volume even up to nonphysiological pressures.;Our results suggest that the structural and mechanical differences demonstrated will have significant influence on several mouse models of lung disease, especially those involving the development of emphysema.