help button home button Am J Pathol R & D Systems
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Purchase Article
Right arrow View Shopping Cart
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Clugston, R. D.
Right arrow Articles by Greer, J. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Clugston, R. D.
Right arrow Articles by Greer, J. J.
(American Journal of Pathology. 2006;169:1541-1549.)
© 2006 American Society for Investigative Pathology
DOI: 10.2353/ajpath.2006.060445

Teratogen-Induced, Dietary and Genetic Models of Congenital Diaphragmatic Hernia Share a Common Mechanism of Pathogenesis

Robin D. Clugston*, Jürgen Klattig{dagger}, Chistoph Englert{dagger}, Margaret Clagett-Dame{ddagger}, Jelena Martinovic§, Alexandra Benachi§ and John J. Greer*

From the Department of Physiology,* University of Alberta, Edmonton, Alberta, Canada; Leibniz Institute for Age Research–Fritz Lipmann Institute,{dagger} Jena, Germany; Department of Biochemistry,{ddagger} University of Wisconsin-Madison, Madison, Wisconsin; and Hopital Necker-Enfants Malades,§ Paris, France

Congenital diaphragmatic hernia (CDH) is a frequently occurring, major congenital abnormality that has high mortality and significant morbidity in survivors. Currently, the pathogenesis of CDH is poorly understood. In this study, we have compared the anatomical characteristics of diaphragm defects in the well-described nitrofen model with the pathogenesis of CDH in vitamin A-deficient rats and wt1 null-mutant mice, representing teratogen-induced, dietary and genetic models of CDH, respectively. Our histological investigations, aided by three-dimensional reconstruction of the developing diaphragm, revealed a common pathogenic mechanism with regards to the location of the diaphragm defect in the foramen of Bochdalek (posterolateral diaphragm) and specific abnormalities within the primordial diaphragm. Furthermore, our analysis of postmortem specimens highlighted similarities in human cases of CDH and these animal models, supporting our hypothesis that CDH in humans arises from a defect in the primordial diaphragm. Immunohistochemical data were consistent with the defect in the primordial diaphragm being in the nonmuscular component. Importantly, these data show that very distinct models of CDH all share a common pathogenic mechanism and, together with supporting evidence from pathological specimens, highlight our proposed pathogenic model for CDH.




This article has been cited by other articles:


Home page
 J. Appl. Physiol.Home page
C. B. Mantilla and G. C. Sieck
Key aspects of phrenic motoneuron and diaphragm muscle development during the perinatal period
J Appl Physiol, June 1, 2008; 104(6): 1818 - 1827.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
R. D. Clugston, W. Zhang, and J. J. Greer
Gene expression in the developing diaphragm: significance for congenital diaphragmatic hernia
Am J Physiol Lung Cell Mol Physiol, April 1, 2008; 294(4): L665 - L675.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Copyright © 2006 by the American Society for Investigative Pathology.