BONE AND HEMATOPOIETIC DEFECTS IN MICE LACKING C-FOS
BONE AND HEMATOPOIETIC DEFECTS IN MICE LACKING C-FOS
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DOI：
10.1038/360741a0
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发表时间：
1992-12-24
期刊：
影响因子：
64.8
通讯作者：
WAGNER, EF
中科院分区：
文献类型：
--
作者：
WANG, ZQ;OVITT, C;WAGNER, EF
原癌基因c-fos是从小鼠骨肉瘤1中分离出来的v-fos的细胞同源物。FOS蛋白是AP-1转录因子复合体的主要组成部分，该复合体包括Jun家族成员2。C-fos在小鼠发育中的骨骼和牙齿、造血细胞、生殖细胞和中枢神经系统3-11中稳定表达。已有研究表明，c-fos在信号转导、细胞增殖和分化中具有重要作用。我们之前已经证明，c-fos在转基因和嵌合体小鼠中的过度表达特异性地影响骨、软骨和造血细胞的发育16-20。为了更好地了解c-fos在体内的功能，我们利用胚胎干细胞中的基因打靶来产生细胞和缺乏c-fos的小鼠。在这里，我们报告杂合子FOS+/-小鼠看起来正常，尽管雌性小鼠表现出扭曲的传播频率。所有纯合子fos-/-小鼠都是生长迟缓的，发展成骨化病，骨骼重塑和牙齿萌出缺陷，并改变了造血。这些数据将c-Fos蛋白定义为特定细胞间隔发育所必需的分子。
THE proto-oncogene c-fos is the cellular homologue of v-fos originally isolated from murine osteosarcoma1. Fos protein is a major component of the AP-1 transcription factor complex, which includes members of the jun family2. Stable expression of c-fos in mice has been demonstrated in developing bones and teeth, haematopoietic cells, germ cells and in the central nervous system3-11. It has been proposed that c-fos has an important role in signal transduction, cell proliferation and differentiation12-15. We have previously demonstrated that overexpression of c-fos in transgenic and chimaeric mice specifically affects bone, cartilage and haematopoietic cell development16-20. To understand better the function of c-fos in vivo, we used gene targeting in embryonic stem cells to generate cells and mice lacking c-fos. Here we report that heterozygous fos +/- mice appear normal, although females exhibit a distorted transmission frequency. All homozygous fos -/- mice are growth-retarded, develop osteopetrosis with deficiencies in bone remodelling and tooth eruption, and have altered haematopoiesis. These data define the c-Fos protein as an essential molecule for the development of specific cellular compartments.