Alterations in cell growth and signaling in ErbB3 binding protein-1 (Ebp1) deficient mice.

Alterations in cell growth and signaling in ErbB3 binding protein-1 (Ebp1) deficient mice.
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DOI:
10.1186/1471-2121-9-69
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发表时间:
2008-12-18
期刊:
影响因子:
--
通讯作者:
Hamburger AW
Hamburger AW
中科院分区:
生物3区
文献类型:
--
作者:
Zhang Y;Lu Y;Zhou H;Lee M;Liu Z;Hassel BA;Hamburger AW

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ErbB3结合蛋白-1 (Ebp1)属于与细胞生长、凋亡和分化有关的DNA/RNA结合蛋白家族。然而,Ebp1在整个机体中的生理作用尚不清楚。因此,我们产生了eebp1缺陷小鼠,在eebp1 (pa2g4)基因的内含子2上插入了一个基因陷阱。Ebp1-/-小鼠比野生型和杂合性匹配的幼崽平均小30%。从第10天到第30天,生长明显迟缓。在胚胎成纤维细胞和成年敲除小鼠中,IGF-1的产生以及IGBP-3和igbp - 4蛋白水平均降低。与野生型细胞相比,从第12.5天敲除胚胎中获得的成纤维细胞的增殖能力也有所下降。微阵列表达分析揭示了包括MAPK信号转导通路成员在内的细胞生长重要基因的变化。此外,增殖相关基因如AKT和雄激素受体的表达或激活在体外被证明受Ebp1表达的影响,在成人组织中也发生了改变。这些结果表明,Ebp1可以影响动物模型的生长,但增殖相关基因的表达是细胞和环境特异性的。Ebp1-/-小鼠系为研究Ebp1在整个机体中的功能提供了一种新的体内模型。
The ErbB3 binding protein-1 (Ebp1) belongs to a family of DNA/RNA binding proteins implicated in cell growth, apoptosis and differentiation. However, the physiological role of Ebp1 in the whole organism is not known. Therefore, we generated Ebp1-deficient mice carrying a gene trap insertion in intron 2 of the Ebp1 (pa2g4) gene. Ebp1-/- mice were on average 30% smaller than wild type and heterozygous sex matched littermates. Growth retardation was apparent from Day 10 until Day 30. IGF-1 production and IGBP-3 and 4 protein levels were reduced in both embryo fibroblasts and adult knock-out mice. The proliferation of fibroblasts derived from Day 12.5 knock out embryos was also decreased as compared to that of wild type cells. Microarray expression analysis revealed changes in genes important in cell growth including members of the MAPK signal transduction pathway. In addition, the expression or activation of proliferation related genes such as AKT and the androgen receptor, previously demonstrated to be affected by Ebp1 expression in vitro, was altered in adult tissues. These results indicate that Ebp1 can affect growth in an animal model, but that the expression of proliferation related genes is cell and context specific. The Ebp1-/- mouse line represents a new in vivo model to investigate Ebp1 function in the whole organism.
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