Overexpressing dominant-negative FGFR2-IIIb impedes lung branching morphogenesis in pigs

Qin Chen; 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

doi:10.1016/j.jgg.2018.02.002

Volume 45 Issue 3

Mar. 2018

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Article Navigation > Journal of Genetics and Genomics > 2018 > 45(3): 147-154

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Overexpressing dominant-negative FGFR2-IIIb impedes lung branching morphogenesis in pigs

doi: 10.1016/j.jgg.2018.02.002

Qin Chen^{a, #},
Bin Fang^{a, #},
Ying Wang^{a, b, #},
Chu Li^a,
Xiaoxue Li^a,
Ronggen Wang^a,
Qiang Xiong^a,
Lining Zhang^a,
Yong Jin^a,
Manling Zhang^{a, b},
Xiaorui Liu^a,
Lin Li^{a, b},
Lisha Mou^d,
Rongfeng Li^{a, b},
Haiyuan Yang^{a, b},
Yifan Dai^{a, b, c, d}

a
Jiangsu Key Laboratory of Xenotransplantation, Nanjing Medical University, Nanjing 211166, China
b
Key Laboratory of Targeted Intervention of Cardiovascular Disease, Collaborative Innovation Center for Cardiovascular Disease Translational Medicine, Nanjing Medical University, Nanjing 211166, China
c
State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing 211166, China
d
Shenzhen 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

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Corresponding 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.
- Dominant-negative FGFR2-IIIb,
- Lung organogenesis,
- Porcine

This author contributed equally to this work.

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References(37)

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