Submitted on October 11, 2007
Accepted on January 14, 2008
ErbB4 deletion leads to changes in lung function and structure similar to bronchopulmonary dysplasia
Erkhembulgan Purevdorj1, Katja Zscheppang1, Heinz G Hoymann2, Armin Braun2, Dietlinde von Mayersbach1, Maria-Jantje Brinkhaus3, Andreas Schmiedl4, and Christiane E. L. Dammann5*
1 Pediatric Pulmonology and Neonatology, Hannover Medical School, Hannover, Germany
2 Immunology, Allergology and Immunotoxicology, Fraunhofer ITEM, Hannover, Germany
3 Perinatal Infectious Disease Epidemiology Unit, Hannover Medical School, Hannover, Germany
4 Anatomy, Medical School of Hannover, Hannover, Germany
5 Pediatrics, Tufts-Nemc, Boston, Massachusetts, United States
* To whom correspondence should be addressed. E-mail: cdammann{at}tufts-nemc.org.
Neuregulin is an important growth factor in fetal surfactant synthesis and down regulation 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 to14 weeks 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 down regulation 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.
