Compensation by fibroblast growth factor 1 (FGF1) does not account for the mild phenotypic defects observed in FGF2 null mice
Compensation by fibroblast growth factor 1 (FGF1) does not account for the mild phenotypic defects observed in FGF2 null mice
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DOI：
10.1128/mcb.20.6.2260-2268.2000
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发表时间：
2000-03-01
影响因子：
5.3
通讯作者：
Basilico, C
中科院分区：
文献类型：
--
作者：
Miller, DL;Ortega, S;Basilico, C
成纤维细胞生长因子1（FGF 1）和FGF 2是FGF家族的原型成员，参与多种生理和病理过程。与大多数其他FGF不同，FGF1和FGF2是普遍表达的，并且不能有效分泌。小鼠的基因敲除先前已经证明了FGF2在大脑发育，血压调节和伤口愈合中的作用。与FGF2缺失相关的相对轻微的表型缺陷导致了这样的假设，即在这些小鼠中，其他FGF的持续表达部分地补偿了FGF2的缺失。我们现在报道我们的缺乏FGF1的小鼠的产生以及它们与我们先前描述的FGF2缺失小鼠组合以产生缺乏FGF1和FGF2的小鼠的用途。FGF1-FGF2双敲除小鼠是存活的和可生育的，并且不显示任何总体表型缺陷。在双敲除小鼠中，我们观察到的缺陷程度与先前描述的FGF2缺失小鼠相似。观察到额叶运动皮层神经元组织和伤口愈合率的差异。我们还在FGF2（-/-）小鼠和FGF1-FGF2双敲除小鼠中观察到严重程度相似的造血新损伤。在仅缺乏FGF1的小鼠中基本上没有发现异常。我们的研究结果表明，相对温和的缺陷，在FGF2基因敲除的动物是不是一个后果的补偿FGF1和建议高度限制的作用，这两个因素在正常的发育和生理条件下。
Fibroblast growth factor 1 (FGF1) and FGF2, the prototypic members of the FGF family of growth factors, have been implicated in a variety of physiological and pathological processes. Unlike most other FGFs, FGF1 and FGF2 are ubiquitously expressed and are not efficiently secreted. Gene knockouts in mice have previously demonstrated a role for FGF2 in brain development, blood pressure regulation, and wound healing. The relatively mild phenotypic defects associated with FGF2 deletion Led to the hypothesis that the continued expression of other FGFs partially compensated for the absence of FGF2 in these mice, We now report our generation of mice Lacking FGF1 and their use, in combination with our previously described FGF2 null mice, to produce mice lacking both FGF1 and FGF2. FGF1-FGF2 double-knockout mice are viable and fertile and do not display any gross phenotypic defects. In the double-knockout mice we observed defects that were similar in extent to those previously described for the FGF2 null mice. Differences in the organization of neurons of the frontal motor cortex and in the rates of wound healing were observed. We also observed in FGF2(-/-) mice and in FGF1-FGF2 double-knockout mice novel impairments in hematopoiesis that were similar in severity. Essentially no abnormalities were found in mice lacking only FGF1. Our results suggest that the relatively mild defects in FGF2 knockout animals are not a consequence of compensation by FGF1 and suggest highly restricted roles for both factors under normal developmental and physiological conditions.