Zhang Yuexing, Lu Yan, Zhou Hua, Lee Myounghee, Liu Zhenqiu, Hassel Bret A, Hamburger Anne W
Department of Pathology, University of Maryland School of Medicine, Baltimore, MD, USA.
BMC Cell Biol. 2008 Dec 18;9:69. doi: 10.1186/1471-2121-9-69.
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.
埃布B3结合蛋白1（Ebp1）属于一个DNA/RNA结合蛋白家族，参与细胞生长、凋亡和分化过程。然而，Ebp1在整个生物体中的生理作用尚不清楚。因此，我们构建了Ebp1基因（pa2g4）第2内含子携带基因陷阱插入的Ebp1基因敲除小鼠。
Ebp1基因敲除小鼠平均比野生型及性别匹配的杂合子同窝小鼠小30%。从第10天到第30天，生长迟缓明显。胚胎成纤维细胞和成年基因敲除小鼠中IGF-1的产生以及IGBP-3和4的蛋白水平均降低。与野生型细胞相比，来自第12.5天基因敲除胚胎的成纤维细胞增殖也减少。微阵列表达分析揭示了细胞生长相关重要基因的变化，包括丝裂原活化蛋白激酶（MAPK）信号转导通路的成员。此外，之前在体外已证明受Ebp1表达影响的增殖相关基因如AKT和雄激素受体的表达或激活在成年组织中发生了改变。
这些结果表明Ebp1可在动物模型中影响生长，但增殖相关基因的表达具有细胞和环境特异性。Ebp1基因敲除小鼠品系代表了一种研究Ebp1在整个生物体中功能的新型体内模型。
