Adenoviral‐mediated expression of antisense RNA to fibroblast growth factors disrupts murine vascular development
Adenoviral‐mediated expression of antisense RNA to fibroblast growth factors disrupts murine vascular development
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腺病毒介导的成纤维细胞生长因子反义RNA表达破坏小鼠血管发育
作者：
I. Leconte;J. C. Fox;H. Baldwin;C. Buck;J. L. Swain
成纤维细胞生长因子(FGFs)在发育中的胚胎中表达，被认为调节胚胎和血管的生长。本研究的目的是阐明碱性成纤维细胞生长因子(FGF-2)在小鼠胚胎心血管发育中的作用。12小时后，将携带β-半乳糖苷酶或反义成纤维细胞生长因子-2RNA的复制缺陷型腺病毒(0.5×10~6个空斑形成单位)注射到培养胚胎的静脉窦内。在接下来的12小时内，只接受表达β-半乳糖苷酶基因的复制缺陷型腺病毒的胚胎继续正常发育。相比之下，尽管胚胎心脏继续跳动，但接受携带反义成纤维细胞生长因子-2 RNA的腺病毒的受试者表现出明显的形态发生异常，包括生长停止和卵黄囊血管发育异常。显微血管造影术和组织学检查证实卵黄囊血管发育异常。在正义方向联合注射携带成纤维细胞生长因子-2基因的病毒可逆转反义成纤维细胞生长因子-2 RNA表达的影响。这些结果证实了复制缺陷型腺病毒将基因表达靶向发育中的血管系统的有效性，并为成纤维细胞生长因子在早期胚胎正常的血管组装中发挥关键作用提供了证据。反义成纤维细胞生长因子-2的表达导致胚胎生长停止，很可能是由于早期胚胎血细胞从卵黄囊进入胚胎的有效循环失败。戴夫。戴恩。1998年；213：421-430。©1998 Wiley-Liss，Inc.
Fibroblast growth factors (FGFs) are expressed in the developing embryo and are postulated to regulate embryonic and vascular growth. The goal of this study was to elucidate the role of basic fibroblast growth factor (FGF‐2) in early murine embryonic cardiovascular development in the mouse embryo. Gestation day 7.5 embryos were harvested and placed in culture, and 12 hr later replication‐defective adenovirus (0.5 × 106 plaque forming units) encoding either β‐galactosidase or antisense FGF‐2 RNA was injected into the sinus venosus of the cultured embryos. Embryos receiving only replication‐defective adenovirus expressing the β‐galactosidase gene continued to develop normally over the next 12 hr. In contrast, those receiving adenovirus encoding antisense FGF‐2 RNA displayed marked morphogenetic abnormalities, including cessation of growth and abnormal yolk sac vascular development, even though the embryonic hearts continued to beat. Abnormal development of the yolk sac vasculature was confirmed by microangiography and by histologic examination. Coinjection of virus carrying FGF‐2 cDNA in the sense orientation reversed the effects of antisense FGF‐2 RNA expression. These results confirm the efficacy of the replication‐defective adenovirus for targeting gene expression to the developing vasculature and provide evidence for a critical role of FGF in the normal vascular assembly in the early embryo. Cessation of embryonic growth on expression of antisense FGF‐2 RNA was most likely attributable to failure of efficient circulation of the early embryonic blood cells from the yolk sac into the embryo. Dev. Dyn. 1998;213:421–430. © 1998 Wiley‐Liss, Inc.
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影响因子：
4.6
作者：
O. Haub;M. Goldfarb
通讯作者：
O. Haub;M. Goldfarb
影响因子：
4.4
作者：
E. P. Kay;Xin Gu;Ronald E. Smith
通讯作者：
E. P. Kay;Xin Gu;Ronald E. Smith
DOI：
10.1073/pnas.90.10.4601
发表时间：
1993-05
影响因子：
11.1
作者：
Yiping Yang;S. Raper;J. Cohn;J. Engelhardt;J. M. Wilson
通讯作者：
Yiping Yang;S. Raper;J. Cohn;J. Engelhardt;J. M. Wilson
影响因子：
4.6
作者：
L. Niswander;G. Martin
通讯作者：
L. Niswander;G. Martin
DOI：
10.1073/pnas.88.8.3441
发表时间：
1991-04-01
影响因子：
11.1
作者：
ERIKSSON, AE;COUSENS, LS;MATTHEWS, BW
通讯作者：
MATTHEWS, BW