[Generation of transgenic animals, expressing alpha- and beta-chains of autoreactive TCR].
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.
Zvezdova
E S
ES
Silaeva
Iu Iu
IuIu
Vagida
M S
MS
Mariukhnich
E V
EV
Deĭkin
A V
AV
Ermolkevich
T G
TG
Kadulin
S G
SG
Sadchikova
E R
ER
Gol'dman
I L
IL
Kazanskiĭ
D B
DB
D000818:Animals; D001327:Autoimmune Diseases / Q000235:genetics* / Q000276:immunology / Q000378:metabolism* / Q000628:therapy; D003001:Cloning, Molecular; D004195:Disease Models, Animal; D015870:Gene Expression; D006649:Histocompatibility Antigens / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D006801:Humans; D006825:Hybridomas; D051379:Mice; D008822:Mice, Transgenic; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000096:biosynthesis* / Q000235:genetics* / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D019076:Transgenes / Q000235:genetics / Q000276:immunology*
D006649:Histocompatibility Antigens; D016693:Receptors, Antigen, T-Cell, alpha-beta