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Induction of various autoantibodies by mutant gene lpr in several strains of mice

Kelley, V. E.
Masuda, K.
Yoshida, Haruyoshi
Roths, J. B.
Murphy, E. D.
Published in The Journal of immunology. 1984, vol. 133, no. 1, p. 227-233
Abstract The effect of the autosomal mutant gene lpr (lymphoproliferation) on the development of various autoantibodies and immune complex (IC) glomerulonephritis was investigated in four genetically distinct strains of mice: MRL/ MpJ, C3H/HeJ, C57BL/6J, and AKR/J. The presence of the lpr gene not only enhanced the production of autoantibodies in the autoimmune MRL/ MpJ strain, but also induced the formation of various kinds of autoantibodies in the three other strains of mice without any apparent predisposition to autoimmune disease. Autoantibodies induced by the lpr gene included anti-double-stranded DNA, anti-single-stranded DNA, anti-IgG, anti-thymocyte, and anti-serum glycoprotein gp70. This indicates that the action of the lpr gene on the development of autoantibody response does not require the particular abnormalities of the MRL genome. The differences in amounts and types of autoantibodies among the lpr strains reflect the difference in the background genome of each strain, suggesting the participation of other genes or factors determining the quantity and/or specificity of autoantibodies. In addition to the development of autoantibodies, the three nonautoimmune strains of mice produced high levels of unidentified IC in the presence of the lpr gene, detectable by the C1q and the conglutinin binding tests. Their glomerular lesions, however, were relatively limited when compared with MRL/ MpJ -lpr/lpr mice, which developed severe glomerulonephritis early in their life. These results suggest that the lpr gene is able to induce the formation of various autoantibodies and IC at significant concentrations in nonautoimmune mice, but for the full manifestation of systemic lupus erythematosus there may be a requirement for supplemental genetic abnormalities or factors.
Keywords AnimalsAntigen-Antibody Complex/analysis/metabolism/physiologyAntilymphocyte Serum/pharmacologyAutoantibodies/ biosynthesisCollectinsComplement Activating Enzymes/metabolismComplement C1qDNA, Single-Stranded/immunologyFemaleGenes, RecessiveGlomerulonephritis/genetics/immunology/pathologyImmunoglobulin G/biosynthesis/immunologyLymphocyte ActivationMiceMice, Inbred AKRMice, Inbred C3HMice, Inbred C57BLMice, Mutant StrainsSerum Globulins/metabolism
PMID: 6609979
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IZUI, Shozo et al. Induction of various autoantibodies by mutant gene lpr in several strains of mice. In: The Journal of immunology, 1984, vol. 133, n° 1, p. 227-233.

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Deposited on : 2010-08-27

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