Genetically Modified Mouse Models of Congenital Diaphragmatic Hernia: Opportunities and Limitations for Studying Altered Lung Development

Abstract

Congenital diaphragmatic hernia (CDH) is a relatively common and life-threatening birth defect, characterized by an abnormal opening in the primordial diaphragm that interferes with normal lung development. As a result, CDH is accompanied by immature and hypoplastic lungs, being the leading cause of morbidity and mortality in patients with this condition. In recent decades, various animal models have contributed novel insights into the pathogenic mechanisms underlying CDH and associated pulmonary hypoplasia. In particular, the generation of genetically modified mouse models, which show both diaphragm and lung abnormalities, has resulted in the discovery of multiple genes and signaling pathways involved in the pathogenesis of CDH. This article aims to offer an up-to-date overview on CDH-implicated transcription factors, molecules regulating cell migration and signal transduction as well as components contributing to the formation of extracellular matrix, whilst also discussing the significance of these genetic models for studying altered lung development with regard to the human situation.

Disruptions in retinoic acid signaling pathway contribute to abnormal lung development in congenital diaphragmatic hernia: a therapeutic potential for retinoids to attenuate pulmonary hypoplasia

“…Most of our current knowledge about the pathogenesis of CDH and associated morphological changes in hypoplastic lungs has originated from experimental animal models. 6 Nevertheless, the molecular and cellular mechanisms underlying CDH and PH remain poorly understood.…”