[Generation of transgenic animals, expressing alpha- and beta-chains of autoreactive TCR]

Mol Biol (Mosk). 2010 Mar-Apr;44(2):311-22.
[Article in Russian]

Abstract

Transgenic animal studies has become a key approach for gene function analysis as well as for modeling of different human diseases, including autoimmune diseases caused by activation of T-lymphocyte clones whose TCRs possesses high affinity for syngeneic MHC molecules. In this study we cloned genes, encoding alpha- and beta- chains of autoreactive TCR of hybridoma 7, specific for syngeneic MHC class II molecules A(b). Amplified DNA fragments, containing rearranged genomic DNA of alpha- and beta-chains of hybridoma 7 were cloned into special cassette vectors, containing natural promoter and enhancer elements for direct expression of genes encoding TCR alpha- and beta-chains in T-lymphocytes of transgenic animals. Using this cassette vectors we generated animals in which most of peripheral T-lymphocytes carry alpha-chain, as well as animals with expression of beta-chain transgene of autoreactive TCR. Obtained animals may serve to explain a number of intrathymic selection processing features and T cell maturation as well as to serve as experimental models for development of new approaches to therapy of autoimmune diseases.

Publication types

  • English Abstract
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autoimmune Diseases / genetics*
  • Autoimmune Diseases / immunology
  • Autoimmune Diseases / metabolism*
  • Autoimmune Diseases / therapy
  • Cloning, Molecular
  • Disease Models, Animal
  • Gene Expression*
  • Histocompatibility Antigens / genetics
  • Histocompatibility Antigens / immunology
  • Histocompatibility Antigens / metabolism
  • Humans
  • Hybridomas
  • Mice
  • Mice, Transgenic
  • Receptors, Antigen, T-Cell, alpha-beta / biosynthesis*
  • Receptors, Antigen, T-Cell, alpha-beta / genetics*
  • Receptors, Antigen, T-Cell, alpha-beta / immunology
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism*
  • Transgenes / genetics
  • Transgenes / immunology*

Substances

  • Histocompatibility Antigens
  • Receptors, Antigen, T-Cell, alpha-beta