作为创新转基因和基因敲除生物模型的一种推广手段,用于获得具有 HLA-C*07:02:01:01 基因的人源化转基因小鼠的基因工程构建原理

N. Karkischenko, V. N. Lazarev, V. A. Manuvera, P. Bobrovsky, N. V. Petrova, E. Koloskova, E. S. Glotova
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引用次数: 0

摘要

不同人群的基因差异会影响药物的作用机制和疗效。考虑到不同个体基因多态性特点的生物模型可以更全面地研究药剂(包括免疫生物学药剂)的分子遗传作用机制。重组 DNA 编码一种混合 MHC I 类蛋白,该蛋白含有融合了 HLA-C*07:02:01:01 分子的抗原递呈结构域(α1 和 α2 结构域)和小鼠 H2 复合物的 α3 结构域的人类 ß2 微小球蛋白。纯化的线性化 DNA 片段含有目标构建体,其两侧有确保其稳定转录的调控片段,用于获得新的人源化转基因小鼠品系。通过编码含有抗原递呈结构域 HLA-C*07:02:01:01 的嵌合 MHC I 类蛋白来设计人源化转基因小鼠的原理与获得 HLA-А*02:01:01 和 HLA-B*18:01:01:02 人源化转基因品系小鼠的原理相似。这些实验室小鼠转基因品系是独立的生物模型,也可用作获得相应转基因品系和基因敲除品系的基线。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Principles of Creation of a Genetic Engineering Construction for Obtaining Humanized Transgenic Mice with HLA-C*07:02:01:01, as a Promote of Innovative Transgenic and Knockout Biomodels
Genetic differences in different populations influence the mechanism and efficacy of drugs. Biomodels that take into account the peculiarities of genetic polymorphism in different individuals allow to more fully investigate the molecular-genetic mechanisms of action of pharmacological agents, including immunobiological ones. Recombinant DNA encoding a hybrid MHC class I protein containing human ß2-microglobulin fused with antigen-presenting domains (α1 and α2 domains) of the HLA-C*07:02:01:01 molecule and α3 domain of the mouse H2-complex was created. The purified linearized DNA fragment containing the target construct flanked by regulatory fragments ensuring its stable transcription was used to obtain a new line of humanized transgenic mice. The principles of designing humanized transgenic mice by encoding a chimeric MHC class I protein containing antigen-presenting domains HLA-C*07:02:01:01 are similar to those for obtaining mice of the HLA-А*02:01:01 and HLA-B*18:01:01:02 humanized transgenic lines. These transgenic lines of laboratory mice are independent biomodels, and also be used as baselines for obtaining corresponding transgenic and knockout lines.
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