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携带102 kb BAC基因组片段的转基因小鼠中牛新生Fc受体α链的位置独立和拷贝数相关表达

Position independent and copy-number-related expression of the bovine neonatal Fc receptor alpha-chain in transgenic mice carrying a 102 kb BAC genomic fragment.

作者信息

Bender Balázs, Bodrogi Lilla, Mayer Balázs, Schneider Zita, Zhao Yaofeng, Hammarström Lennart, Eggen André, Kacskovics Imre, Bosze Zsuzsanna

机构信息

Agricultural Biotechnology Center, 2100, Szent-Györgyi A. st.4, Godollo, Hungary.

出版信息

Transgenic Res. 2007 Oct;16(5):613-27. doi: 10.1007/s11248-007-9108-9. Epub 2007 Jun 27.

DOI:10.1007/s11248-007-9108-9
PMID:17594529
Abstract

We generated and characterized transgenic mice carrying a 102 kb bovine genomic fragment, encoding the neonatal Fc receptor alpha-chain (bFcRn). FcRn plays a crucial role in the maternal IgG transport and it also regulates the IgG and albumin homeostasis. Some of its functions and transcriptional regulation show species specific differences. The FcRn heterodimer is composed of the alpha-chain and beta-2-microglobulin (beta2 m). A bacterial artificial chromosome containing the bovine FcRn alpha-chain gene (bFCGRT) with its 44 kb 5' and 50 kb long 3' flanking sequences was microinjected into fertilized mouse oocytes. Two of the transgenic lines generated, showed copy number related and integration site independent bFcRn expression. The bFcRn alpha-chain forms a functional receptor with the mouse beta2-microglobulin and extends the half-life of the mouse IgG in transgenic mice. Our results underline the feasibility of creating BAC transgenic mouse models of economically important bovine genes.

摘要

我们构建并鉴定了携带102 kb牛基因组片段的转基因小鼠,该片段编码新生Fc受体α链(bFcRn)。FcRn在母体IgG转运中起关键作用,还调节IgG和白蛋白的体内平衡。其一些功能和转录调控存在物种特异性差异。FcRn异二聚体由α链和β2微球蛋白(β2m)组成。将含有牛FcRnα链基因(bFCGRT)及其44 kb 5'和50 kb长3'侧翼序列的细菌人工染色体显微注射到受精的小鼠卵母细胞中。所产生的两个转基因品系显示出与拷贝数相关且与整合位点无关的bFcRn表达。bFcRnα链与小鼠β2微球蛋白形成功能性受体,并延长了转基因小鼠体内小鼠IgG的半衰期。我们的结果强调了创建具有经济重要性的牛基因的BAC转基因小鼠模型的可行性。

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Position independent and copy-number-related expression of the bovine neonatal Fc receptor alpha-chain in transgenic mice carrying a 102 kb BAC genomic fragment.携带102 kb BAC基因组片段的转基因小鼠中牛新生Fc受体α链的位置独立和拷贝数相关表达
Transgenic Res. 2007 Oct;16(5):613-27. doi: 10.1007/s11248-007-9108-9. Epub 2007 Jun 27.
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FcRn Overexpression Expands Diversity of the Humoral Immune Response in bFcRn Transgenic Mice.FcRn 过表达扩展了 bFcRn 转基因小鼠体液免疫反应的多样性。
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本文引用的文献

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Enhanced half-life of genetically engineered human IgG1 antibodies in a humanized FcRn mouse model: potential application in humorally mediated autoimmune disease.在人源化FcRn小鼠模型中基因工程改造的人IgG1抗体半衰期延长:在体液介导的自身免疫性疾病中的潜在应用。
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Overexpression of Bovine FcRn in Mice Enhances T-Dependent Immune Responses by Amplifying T Helper Cell Frequency and Germinal Center Enlargement in the Spleen.牛FcRn在小鼠中的过表达通过增加脾脏中辅助性T细胞频率和生发中心扩大来增强T细胞依赖性免疫反应。
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NFκB induces overexpression of bovine FcRn: a novel mechanism that further contributes to the enhanced immune response in genetically modified animals carrying extra copies of FcRn.核因子κB诱导牛FcRn的过表达:一种有助于携带额外FcRn拷贝的转基因动物增强免疫反应的新机制。
MAbs. 2013 Nov-Dec;5(6):860-71. doi: 10.4161/mabs.26507.
7
Transgenic rabbits that overexpress the neonatal Fc receptor (FcRn) generate higher quantities and improved qualities of anti-thymocyte globulin (ATG).过度表达新生Fc受体(FcRn)的转基因兔能产生数量更多、质量更好的抗胸腺细胞球蛋白(ATG)。
PLoS One. 2013 Oct 23;8(10):e76839. doi: 10.1371/journal.pone.0076839. eCollection 2013.
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Influence of FCGRT gene polymorphisms on pharmacokinetics of therapeutic antibodies.FCGRT 基因多态性对治疗性抗体药代动力学的影响。
MAbs. 2013 Jul-Aug;5(4):614-9. doi: 10.4161/mabs.24815. Epub 2013 Apr 25.
9
FcRn overexpression in transgenic mice results in augmented APC activity and robust immune response with increased diversity of induced antibodies.转基因小鼠中 FcRn 的过表达导致 APC 活性增强,产生强烈的免疫应答,并诱导产生多样性增加的抗体。
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Perspectives on immunoglobulins in colostrum and milk.对初乳和母乳中免疫球蛋白的看法。
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Kinetics of FcRn-mediated recycling of IgG and albumin in human: pathophysiology and therapeutic implications using a simplified mechanism-based model.
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