Bin Fang
Ying Wang
Chu Li
Xiaoxue Li
Ronggen Wang
Qiang Xiong
Lining Zhang
Yong Jin
Manling Zhang
Xiaorui Liu
Lin Li
Lisha Mou
Rongfeng Li
Haiyuan Yang
Yifan Dai
aJiangsu Key Laboratory of Xenotransplantation, Nanjing Medical University, Nanjing 211166, China
bKey Laboratory of Targeted Intervention of Cardiovascular Disease, Collaborative Innovation Center for Cardiovascular Disease Translational Medicine, Nanjing Medical University, Nanjing 211166, China
cState Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing 211166, China
dShenzhen Xenotransplantation Medical Engineering Research and Development Center, Institute of Translational Medicine, Shenzhen Second People's Hospital, First Affiliated Hospital of Shenzhen University, Shenzhen 518035, China
More InformationCorresponding author: E-mail address: hyyang@njmu.edu.cn (Haiyuan Yang);E-mail address: daiyifan@njmu.edu.cn (Yifan Dai)
Received Date: 2017-11-17
Accepted Date:2018-02-02
Rev Recd Date:2018-01-16
Available Online: 2018-02-14 Publish Date:2018-03-20
Abstract
Abstract
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
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