Distinctive expression of lprcg in the heterozygous state on different genetic backgrounds.
Much knowledge of the etiopathogenesis of human autoimmune diseases has been obtained from the mutant mouse models carrying lpr and gld. These autoimmune genes have been regarded as autosomal recessive. The novel lymphoproliferative and autoimmune mutation lprcg is unique in its interaction with gld despite their different chromosomal locations: chromosomes 19 and 1, respectively. Both lprcg and lpr mutations are shown to be the defects in the Fas antigen gene that controls apoptosis. Evidence has been provided for the partial expression of lpr in the heterozygous state and the significant influences of background genes on lpr-induced autoimmune disorders. To investigate the expression of the heterozygous lprcg and the effects of background genes on it, anatomical, serological, and pathological manifestations were compared among lprcg/lprcg,lprcg/+, and +/+ mice on both MRL/MpJ (MRL) and CBA/KlJms (CBA) backgrounds. On the MRL background, lymph nodes (LN) and spleens of lprcg/+ were significantly larger in weight than those of +/+, but far lower than those of lprcg/lprcg mice. In accord with this, these lprcg/+ mice had intermediate levels of anti-single-stranded DNA antibodies, circulating immune complexes, and serum Igs between those of lprcg/lprcg and +/+ mice and were similar to lprcg/lprcg mice in severity of glomerulonephritis. However, accumulation of anomalous CD4-8- T cells characteristic of the lpr disease was not proved in the enlarged lprcg/+ LN. On the CBA background, the LN and spleen weight increases in lprcg/+ were statistically significant compared to +/+ mice but were minimal, being regarded as clinically insignificant. In support of this, lprcg/+ mice were not different from +/+ mice in any of the serological and pathological parameters examined. The results clearly demonstrate that the lprcg gene can function to induce autoimmune disorders in the heterozygous state on the MRL but not on the CBA background.
Department of Infectious Diseases, University of Tokyo, Japan.
Y
Y
Ogata
M
M
Kimura
K
K
Shimada
T
T
Wakabayashi
H
H
Onoda
T
T
Katagiri
A
A
Matsuzawa
D000818:Animals; D000974:Antibodies, Antinuclear / Q000097:blood; D000936:Antigen-Antibody Complex / Q000097:blood; D001327:Autoimmune Diseases / Q000235:genetics* / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D005786:Gene Expression Regulation; D006579:Heterozygote; D007136:Immunoglobulins / Q000097:blood; D007678:Kidney Glomerulus / Q000276:immunology / Q000473:pathology; D008198:Lymph Nodes / Q000276:immunology / Q000473:pathology; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D008815:Mice, Inbred Strains; D009154:Mutation; D009929:Organ Size; D013154:Spleen / Q000276:immunology / Q000473:pathology
D000974:Antibodies, Antinuclear; D000936:Antigen-Antibody Complex; D007136:Immunoglobulins