Impaired distal airway development in mice lacking elastin

Elastin is a major component of the mammalian lung, predominantly found in the alveoli. Destruction of alveolar elastic fibers is implicated in the pa thogenic mechanism of emphysema in adults. These data define a role for ela stin in the structure and function of the mature lung, and suggest that ela stin is important for alveogenesis. To investigate the role of elastin in l ung development, we examined mice lacking elastin (Eln-/-). At birth, the d istal air sacs of Eln-/- lungs dilate to form abnormally large cavities. Th is phenotype appears before the synthesis and deposition of alveolar elasti n, a process mediated by myofibroblasts and initiated after postnatal Day 4 . Morphometric analyses demonstrate that the perinatal development of termi nal airway branches is arrested in Eln-/- mice. The branching defect is acc ompanied by fewer distal air sacs that are dilated with attenuated tissue s eptae, a condition reminiscent of emphysema. Elastin expression in the lung parenchyma before alveogenesis is localized to the mesenchyme surrounding the developing airways, supporting a role for elastin in airway branching. Thus, in addition to its role in the structure and function of the mature l ung, elastin is essential for pulmonary development and is important for te rminal airway branching.