Thoracic volume reduction as a mechanism for pulmonary hypoplasia in chondrodystrophic mice

Day-18 fetal mice with chondrodysplasia (CHO) have been shown to have pulmonary hypoplasia and thoracic volume reduction, and it has been hypothesized that the former is a secondary effect of the latter. To establish a pathogenetic relationship between thoracic volume reduction and pulmonary hypoplasia, it must first be demonstrated that the decrease in thoracic volume precedes or coincides with the morphologic effect on the lungs. At 24-h intervals through gestation days 14 to 18, the thoracic volume and lung histopathology for normal and chondrodystrophic fetuses were estimated by image analysis of frontal histologic sections. Relative to normal littermates, the average thoracic volumes of day-16, day-17, and day-18 mutants were significantly decreased by 18%, 34%, and 49%, respectively. In the mutants' lungs the histology was normal through day 16, but on days 17 and 18 the frequency of the more distended primary saccules and the amount of potential airspace were decreased relative to normal. These results support the hypothesis that the relative decrease in thoracic volume of the mutant precedes the departure from normal for primary saccule development. The reduction effect on thoracic volume therefore is pathogenetically related to the hypoplastic lungs of fetal mice with lethal chondrodystrophy.