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

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)

This author contributed equally to this work.

摘要

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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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doi: 10.1016/j.jgg.2018.02.002

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

Corresponding author: E-mail address: hyyang@njmu.edu.cn (Haiyuan Yang); E-mail address: daiyifan@njmu.edu.cn (Yifan Dai)

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doi: 10.1016/j.jgg.2018.02.002

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

Corresponding author: E-mail address: hyyang@njmu.edu.cn (Haiyuan Yang); E-mail address: daiyifan@njmu.edu.cn (Yifan Dai)

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