Delineation of a defect in T cell receptor β genes of NZW mice predisposed to autoimmunity

• Published in: The Journal of experimental medicine 1986-03, Vol.163 (3), p.644-653
• Main Authors: NOONAN, D. J, KOFLER, R, SINGER, P. A, CARDENAS, G, DIXON, F. J, THEOFILOPOULOS, A. N
• Format: Article
• Language: English
• Subjects: Animals; Autoimmune Diseases - genetics; Autoimmunity (experimental aspects and models); Base Sequence; Biological and medical sciences; Chromosome Deletion; Chromosome Mapping; DNA Restriction Enzymes; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Genes; Genetic Linkage; Mice; Mice, Inbred Strains - genetics; Mice, Inbred Strains - immunology; Polymorphism, Genetic; Receptors, Antigen, T-Cell - genetics
• ISSN: 0022-1007; 1540-9538
• DOI: 10.1084/jem.163.3.644

In an attempt to determine whether genes involved in T cell antigen recognition are structurally abnormal and thereby promote murine systemic lupus, we analyzed the structural integrity of the D, J, and C region elements of the T cell receptor alpha and beta chain genes in all major lupus strains and several normal strains. Within the limits of restriction fragment length polymorphism analysis, all strains had an identical genomic organization, except the NZW mice, in which a deletion of the C beta 1-D beta 2-J beta 2 elements was found. Sequence analysis of NZW genomic elements containing this deletion placed its probable origin within the first exon of C beta 1, and extending to a complementary region within the first exon of C beta 2. The significance of this abnormality in the pathogenesis of systemic autoimmune disease remains to be determined.