Evidence for the Presence of β2m hom Target Proteins and HLA in Humanized Transgenic Mice of HLA-A*02:01, HLA-B*07:02, and HLA-C*07:02 Lines

V. Karkischenko, A. G. Berzina, N. V. Petrova, I. A. Pomytkin, E. S. Glotova, D. V. Petrov, L. A. Taboyakova, L. A. Bolotskih, N. А. Laryushina
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Abstract

Human leukocyte antigen plays a primary role in the formation of immune response and pathogenesis of   diseases of various etiologies, including the development of negative side effects induced by pharmacological agents. Modern pharmacosafety standards require improvement of existing test systems to conduct high-quality preclinical studies. A number of humanized transgenic mouse lines with hybrid HLA I class molecules on the cell surface, which correspond to the human allelic variants HLA-A*02:01, HLA-B*07:02, and  HLA-C*07:02, were developed at the Scientific Center of Biomedical Technologies of the Federal Medical and Biological Agency of Russia. In this article, we present experimental data on quantitative determination of β2-microglobulin protein and HLA by the “sandwich” ELISA method in mice with different alleles of   HLA I class genes. The results obtained confirm the presence of target functional proteins (transgenicity) in humanized transgenic mice, which is consistent with our previous data obtained when determining the primary sequence of the transgene using Sanger sequencing. We also discuss the scientific and practical significance of such biomodels, as well as the scope of their application.
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在 HLA-A*02:01、HLA-B*07:02 和 HLA-C*07:02 株系人源化转基因小鼠中存在 β2m hom 靶蛋白和 HLA 的证据
人类白细胞抗原在免疫反应的形成和各种病因疾病的发病机制中发挥着主要作用,包括药理制剂诱发的负面副作用。现代药物安全标准要求改进现有的试验系统,以开展高质量的临床前研究。俄罗斯联邦医学和生物局生物医学技术科学中心开发了一些细胞表面具有混合 HLA I 类分子的人源化转基因小鼠品系,这些品系对应于人类等位基因变体 HLA-A*02:01、HLA-B*07:02 和 HLA-C*07:02。本文介绍了采用 "夹心 "ELISA 法定量检测 HLA I 类基因不同等位基因小鼠体内 β2-微球蛋白和 HLA 的实验数据。结果证实人源化转基因小鼠体内存在目标功能蛋白(转基因性),这与我们之前利用桑格测序法确定转基因主序列时获得的数据一致。我们还讨论了此类生物模型的科学和实用意义及其应用范围。
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