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利用免疫球蛋白重链增强子在转基因小鼠中实现基因表达的B淋巴细胞靶向

B-lymphocyte targeting of gene expression in transgenic mice with the immunoglobulin heavy-chain enhancer.

作者信息

Gerlinger P, LeMeur M, Irrmann C, Renard P, Wasylyk C, Wasylyk B

出版信息

Nucleic Acids Res. 1986 Aug 26;14(16):6565-77. doi: 10.1093/nar/14.16.6565.

Abstract

A hybrid gene containing rabbit beta-globin structural sequences (-9 to +1650), and a chicken conalbumin gene promoter (+62 to -102) in the place of the beta-globin promoter (upstream from -9), was inactive in 5 different transgenic mouse line. Adding the mouse immunoglobulin heavy-chain (IgH) enhancer to this construction specifically stimulated expression in B-cells. These results show that IgH enhancer is specifically active in B-cells. Expression of the hybrid gene was low compared to the endogenous immunoglobulin heavy and light-chain genes. Substituting the mouse immunoglobulin kappa light-chain gene (Ig kappa) promoter (+4 to -800) for the heterologous conalbumin promoter was not sufficient to restore gene expression to level of the endogenous genes. In addition to the reproducible B cell expression, we also found inheritable unexpected expression in certain tissues, which varied from line to line.

摘要

一个杂种基因包含兔β-珠蛋白结构序列(-9至+1650),并且其β-珠蛋白启动子(-9上游)的位置被鸡伴清蛋白基因启动子(+62至-102)取代,在5种不同的转基因小鼠品系中是无活性的。将小鼠免疫球蛋白重链(IgH)增强子添加到该构建体中可特异性刺激B细胞中的表达。这些结果表明IgH增强子在B细胞中具有特异性活性。与内源性免疫球蛋白重链和轻链基因相比,杂种基因的表达较低。用小鼠免疫球蛋白κ轻链基因(Igκ)启动子(+4至-800)取代异源伴清蛋白启动子不足以将基因表达恢复到内源性基因的水平。除了可重复的B细胞表达外,我们还在某些组织中发现了可遗传的意外表达,不同品系之间存在差异。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d74d/311664/85b911922197/nar00285-0228-a.jpg

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