Pulmonary hypoplasia associated with reduced thoracic space in mice with disproportionate micromelia (DMM)

Background: Fetal mice homozygous for the Disproportionate micromelia (Dmm) gene were studied as a model for pulmonary hypoplasia in chondrodystrophy. Methods: Wet weight, dry weight, and biochemical content were determined in excised whole lungs, terminal sac morphology and presence of multilamellar bodies were determined by electron microscopy, and volume of the thoracic space was estimated from paraffin casts. Lung development of the mutant was further assessed in whole organ culture. Results. Compared with normal littermates, the mutant showed a significant decrease (28%) in lung wet weight without showing altered lung dry weight or tissue content of DNA and protein. The terminal sacs of lungs fixed by intratracheal instillation were significantly smaller than normal. However, the lungs appeared to have undergone maturation on schedule since the surfactant precursors, multilamellar bodies, were observed and normal tissue-levels of phospholipid were detected. The volume of the mutant's thorax was markedly reduced. Finally, the mutant's lungs when removed from the fetus prior to the onset of thoracic dystrophy (day 15) and cultured for three days demonstrated that, without the confining influence of a reduced thoracic space, they are capable of development comparable to normal. Conclusions: These findings support the hypothesis that the Dmm mutant can be further studied as a model for human pulmonary hypoplasia associated with chondrodystrophy, and that the relationship between the reduced thorax and the lung disorder is cause-and-effect. © 1994 Wiley-Liss, Inc.