Autoimmunity, apoptosis defects and retroviruses.

摘要: Autoimmune disease in both mice and humans is associated with increased expression of endogenous retroviruses the thymus T cells, loss self-tolerance by cells. The basic genetic defect underlying autoimmune has been identified as a mutation Fas apoptosis antigen MRL-lpr/lpr or ligand C3H-gld/gld mice. In mice, lpr results from 5.3 kb insertion ETn retrotransposon second intron gene. contrast to normal which express 2.2 size cDNA, multiple RNA transcripts ranging 2-10.5 kb. addition, 5.7 full-length transcript highly expressed younger To determine if high was dependent on abnormal expression, CD2-fas transgenic were produced using murine cDNA under regulation CD2 promoter enhancer. This resulted normalization also elimination retrotransposon. regulatory sequence contains potential DNA binding sites found enhancers many genes activated during early cell development including enhancer regions for TCR, CD3 IL-2 genes. Therefore we propose that thymus, after activation, integration gene leads development.