Alterations in alveolar epithelium differentiation and vasculogenesis in lungs of LIF/IGF‐I double deficient embryos

Previous studies on double deficient mice for leukemia inhibitory factor (LIF) and insulin‐like growth factor I (IGF‐I) reported that they died of respiratory failure, with abnormal lung histology and altered expression of pulmonary markers. Here we analyzed prenatal Lif/Igf‐I double mutant mouse embryos to characterize LIF and IGF‐I cooperative roles in distal lung epithelium and vascular maturation. Lungs of IGF‐I‐deficient embryos displayed a higher proportion of type II pneumocytes, less differentiated type I pneumocytes, and failure in alveolar capillary remodeling compared to wild type and LIF‐deficient mice. Lif/Igf‐I double knockout lungs showed aggravated pulmonary hypoplasia, lower airway volume, increased proliferation, and elevated levels of ERK1/2 activation. In addition, their alveoli were collapsed and lined by type II cells. The differentiation of type I cells barely occurred and capillaries remained in the abundant mesenchyme. These results indicate that LIF collaborates with IGF‐I in lung alveolar epithelium and vascular maturation. Developmental Dynamics 235:2040–2050, 2006. © 2006 Wiley‐Liss, Inc.