Pulmonary hypoplasia in the myogenin null mouse embryo

Although fetal breathing movements are required for normal lung development , there is uncertainty concerning the specific effect of absent fetal breat hing movements on pulmonary cell maturation. We set out to evaluate pulmona ry development in a genetically defined mouse model, the myogenin null mous e, in which there is a lack of normal skeletal muscle fibers and thus skele tal muscle movements are absent in utero. Significant decreases were observ ed in lung:body weight ratio and lung total DNA at embryonic days (E)14, E1 7, and E20. Reverse transcriptase/polymerase chain reaction, in situ immuno fluorescence, and electron microscopy revealed early lung cell differentiat ion in both null and wild-type lungs as early as E14. However at E14, myoge nin null lungs had decreased 5'-bromo-2-deoxyuridine incorporation compared with that of wild-type littermates, whereas at E17 and E20, increased Bax immunolabeling and terminal deoxyribonucleotidyl transferase-mediated dUTP- biotin nick-end labeling staining were detected in the myogenin null mice b ut not in the wild-type littermates. These observations highlight the impor tance of skeletal muscle contractile activity in utero for normal lung orga nogenesis. Null mice lacking the muscle-specific transcription factor myoge nin exhibit a secondary effect on lung development such that decreased lung cell proliferation and increased programmed cell death are associated with lung hypoplasia.