Genetic studies with mouse models have shown that fibroblast growth factor receptor 2-IIIb (FGFR2-IIIb) plays crucial roles in lung development and differentiation. To evaluate the effect of FGFR2-IIIb in pig lung development, we employed somatic cell nuclear transfer (SCNT) technology to generate transgenic pig fetuses overexpressing the transmembrane (dnFGFR2-IIIb-Tm) and soluble (dnFGFR2-IIIb-HFc) forms of the dominant-negative human FGFR2-IIIb driven by the human surfactant protein C (SP-C) promoter, which was specifically expressed in lung epithelia. Eight dnFGFR2-IIIb-Tm transgenic and twelve dnFGFR2-IIIb-HFc transgenic pig fetuses were collected from three and two recipient sows, respectively. Repression of FGFR2-IIIb in lung epithelia resulted in smaller lobes and retardation of alveolarization in both forms of dnFGFR2-IIIb transgenic fetuses. Moreover, the dnFGFR2-IIIb-HFc transgenic ones showed more deterioration in lung development. Our results demonstrate that disruption of FGFR2-IIIb signaling in the epithelium impedes normal branching and alveolarization in pig lungs, which is less severe than the results observed in transgenic mice. The dnFGFR2-IIIb transgenic pig is a good model for the studies of blastocyst complementation as well as the mechanisms of lung development and organogenesis.
Keywords: Dominant-negative FGFR2-IIIb; Lung organogenesis; Porcine.
Copyright © 2018 Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, and Genetics Society of China. Published by Elsevier Ltd. All rights reserved.