Scientific Article
previous document  unige:11337  next document
add to browser collection

Effect of genetic background on Ea(d) transgene-mediated protection from murine lupus

Iwamoto, Masahiro
Kobayakawa, T.
Published in Journal of Autoimmunity. 1998, vol. 11, no. 3, p. 241-248
Abstract The expression of a transgenic encoding the I-E alpha-chain, Ea(d), is highly effective in the protection from systemic lupus erythematosus (SLE) in BXSB and (MRL x BXSB)F1 male mice, in which a mutant gene, Yaa (Y-linked autoimmune acceleration), plays a critical role. To gain further insight into the protective role of the Ea(d) transgene, we compared the effect of the transgene in two additional lupus-prone (NZB x BXSB)F1 and (NZW x BXSB)F1 hybrid mice, in which both F1 female mice develop typical SLE in the absence of the Yaa gene and their F1 males bearing the Yaa gene develop a more accelerated form of SLE. Comparative analysis of the clinical development of SLE in these F1 hybrid mice showed that Ea(d) transgene expression was much more effective in the protection from SLE occurring in the F1 females than in their male counterparts. Our results indicate that the Ea(d) transgene is capable of preventing SLE by inhibiting autoimmune responses, independently of the Yaa gene-accelerating effect, and that its protective capacity is strongly influenced by the genetic susceptibility to SLE in individual strains of lupus-prone mice. In addition, this autoimmune inhibitory effect was shown to be selective for IgG, but not IgM, anti-DNA autoantibody production, and is more specific for anti-gp70 autoantibody than for anti-DNA autoantibody. These results favour the hypothesis that the transgene expression may lead to the modulation of self-peptide presentation, thereby preventing excessive T-cell-dependent activation of autoreactive B cells.
Keywords AnimalsAntigen-Antibody Complex/bloodAutoantibodies/bloodAutoimmunity/ geneticsChimeraDNA/immunologyFemaleGene Therapy/ methodsGlycoproteins/bloodHistocompatibility Antigens Class II/biosynthesis/genetics/ therapeutic useLinkage (Genetics)Lupus Nephritis/genetics/ prevention & controlMaleMiceMice, Inbred NZBMice, TransgenicSex Chromosome AberrationsSex FactorsTransgenesY Chromosome
Stable URL
Full text
PMID: 9693972
99 hits and 0 download since 2010-08-27
Export document
Format :
Citation style :