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Am J Physiol Lung Cell Mol Physiol 294: L516-L522, 2008. First published January 18, 2008; doi:10.1152/ajplung.00423.2007
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00423.2007v1
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ErbB4 deletion leads to changes in lung function and structure similar to bronchopulmonary dysplasia

Erkhembulgan Purevdorj,1 Katja Zscheppang,1 Heinz G. Hoymann,2 Armin Braun,2 Dietlinde von Mayersbach,1 Maria-Jantje Brinkhaus,3 Andreas Schmiedl,4 and Christiane E. L. Dammann1,5

1Department of Pediatric Pulmonology and Neonatology, Hannover Medical School, 2Immunology, Allergology and Immunotoxicology, Fraunhofer Institute of Toxicology and Experimental Medicine, 3Perinatal Infectious Disease Epidemiology Unit, Hannover Medical School, and 4Department of Anatomy, Hannover Medical School, Hannover, Germany; 5Department of Pediatrics, Division of Newborn Medicine, Tufts-New England Medical Center, Boston, Massachusetts

Submitted 11 October 2007 ; accepted in final form 14 January 2008

Neuregulin is an important growth factor in fetal surfactant synthesis, and downregulation of its receptor, ErbB4, impairs fetal surfactant synthesis. We hypothesized that pulmonary ErbB4 deletion will affect the developing lung leading to an abnormal postnatal lung function. ErbB4-deleted lungs of 11- to 14-wk-old adult HER4heart mice, rescued from their lethal cardiac defects, were studied for the effect on lung function, alveolarization, and the surfactant system. ErbB4 deletion impairs lung function and structure in HER4heart mice resulting in a hyperreactive airway system and alveolar simplification, as seen in preterm infants with bronchopulmonary dysplasia. It also leads to a downregulation of surfactant protein D expression and an underlying chronic inflammation in these lungs. Our findings suggest that this animal model could be used to further study the pathogenesis of bronchopulmonary dysplasia and might help design protective interventions.

surfactant; lung development; alveolar simplification; hyperreactive airway system


Address for reprint requests and other correspondence: C. E. L. Dammann, Dept. of Pediatrics, Floating Hospital for Children, Tufts-New England Medical Center, 750 Washington St., Boston, MA 02111 (e-mail: cdammann{at}tufts-nemc.org)






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