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 develo...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（dn FGFR2-Ⅲb-Tm） and soluble（dn FGFR2-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 dn FGFR2-Ⅲb-Tm transgenic and twelve dn FGFR2-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 dn FGFR2-Ⅲb transgenic fetuses. Moreover, the dn FGFR2-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 dn FGFR2-Ⅲb transgenic pig is a good model for the studies of blastocyst complementation as well as the mechanisms of lung development and organogenesis.展开更多
基金supported by grants from the National Natural Science Foundation of China(Nos.81570402 and 31701283)the National Key R&D Program of China(2017YFC1103701 and 2017YFC1103702)+3 种基金the Jiangsu Key Laboratory of Xenotransplantation(BM2012116)the Sanming Project of Medicine in Shenzhen(SZSM201412020)the Fund for High Level Medical Discipline Construction of Shenzhen(2016031638)the Shenzhen Foundation of Science and Technology(JCYJ20160229204849975 and GCZX2015043017281705)
文摘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（dn FGFR2-Ⅲb-Tm） and soluble（dn FGFR2-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 dn FGFR2-Ⅲb-Tm transgenic and twelve dn FGFR2-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 dn FGFR2-Ⅲb transgenic fetuses. Moreover, the dn FGFR2-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 dn FGFR2-Ⅲb transgenic pig is a good model for the studies of blastocyst complementation as well as the mechanisms of lung development and organogenesis.
