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

Abstract

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.