Generation and characterization of transgenic mice expressing cobra venom factor
Generation and characterization of transgenic mice expressing cobra venom factor
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DOI：
10.1016/s0161-5890(02)00107-4
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发表时间：
2002-10-01
影响因子：
3.6
通讯作者：
Paul, D
中科院分区：
文献类型：
--
作者：
Andrä, J;Halter, R;Paul, D
眼镜蛇毒因子（CVF）是眼镜蛇毒中的抗补体蛋白，激活补体旁路途径，最终导致补体消耗。在这里，我们描述了CVF转基因小鼠模型的发展。我们产生了含有单链前原CVF的全长cDNA的DNA构建体。CVF的表达由α（1）-抗胰蛋白酶启动子控制，以实现肝脏特异性表达。将线性化的DNA显微注射到小鼠卵巢细胞（品系CD 2F 1（BALB/c x DBA/2 J））中，并分析新生小鼠CVF DNA的稳定整合。在建立转基因后，将小鼠在BALB/c背景中繁殖。在肝脏中检测到CVF mRNA，在一些动物中，在肾脏中检测到CVF mRNA。血清中检测到少量CVF蛋白。CVF转基因小鼠血清补体溶血活性几乎不存在。血浆C3浓度显著降低。CVF转基因动物没有表现出异常表型。他们提供了一种动物模型来研究持续激活长期补体消耗的影响，以及补体在宿主免疫反应和疾病发病机制中的作用。(C)2002爱思唯尔科技有限公司。保留所有权利。
Cobra venom factor (CVF), the anticomplementary protein in cobra venom, activates the alternative complement pathway, eventually leading to complement consumption. Here, we describe the development of a transgenic mouse model for CVF. We generated a DNA construct containing the full-length cDNA for single-chain pre-pro-CVF. Expression of CVF was controlled by the alpha(1)-antitrypsin promoter to achieve liver-specific expression. Linearized DNA was microinjected into murine ovary cells (strain CD2F1 (BALB/c x DBA/2J)) and the newborn mice were analyzed for stable integration of CVF DNA. After establishing the transgene, mice were propagated in a BALB/c background. The CVF mRNA was detected in the liver and, in some animals, in the kidney. CVF protein was detected in small amounts in the serum. Serum complement hemolytic activity in CVF-transgenic mice was virtually absent. The concentration of plasma C3 was significantly reduced. The CVF-transgenic animals show no unusual phenotype. They provide an animal model to study the effect of long-term complement depletion by continued activation, as well as the role of complement in host immune response and pathogenesis of disease. (C) 2002 Elsevier Science Ltd. All rights reserved.