Anti-RNA polymerase I antibodies in sera of MRL lpr/lpr and MRL +/+ autoimmune mice. Correlation of antibody production with delayed onset of lupus-like disease in MRL +/+ mice.

Abstract

Sera from individual MRL/lpr and MRL/++ mice, which develop an autoimmune disease similar to human systemic lupus erythematosus (SLE), were screened over a period of approximately 30 wk for the presence of anti-RNA polymerase I and anti-ssDNA antibodies. Even though onset of the disease is delayed in MRL/++ as compared to MRL/lpr mice, anti-ssDNA antibodies were present in comparable concentrations in the sera of all mice by the age of 6 wk. As observed in sera of human SLE patients, anti-RNA polymerase I antibodies were detected in the sera of all MRL mice. However, unlike the anti-ssDNA antibodies, anti-RNA polymerase I antibodies were detected much later in MRL/++ mice (mean age, 22.8 wk) as compared to MRL/lpr mice (mean age, 9.6 wk). The presence of anti-RNA polymerase I antibodies in sera of MRL mice was thus a much better indicator of disease status than the presence of anti-ssDNA antibodies. The appearance and increase in anti-RNA polymerase I antibodies in the sera of MRL/++ mice correlated (R2 = 0.964) with a precipitous decrease in anti-ssDNA antibodies, starting at about 20 wk of age. These results suggest a possible relationship between the RNA polymerase I and DNA autoimmune reactions.

Immunization of nonautoimmune mice with DNA binding domains of the largest subunit of RNA polymerase I results in production of anti-dsDNA and anti-Sm/RNP antibodies

“…We reported previously that MRL-lpr/lpr and MRL-þ /þ mice produce anti-RNAPI antibodies and that the appearance of these antibodies in the sera correlates with onset of lupus-like disease [5]. In the present report, we have demonstrated that these anti-RNAPI antibodies include those directed against the NT region of RNAPI(S1) (Figure 1), which includes a zinc ion binding domain [39,40] and is capable of binding DNA (unpublished results).…”

Linking susceptibility genes and pathogenesis mechanisms using mouse models of systemic lupus erythematosus

“…MRL/ lpr mice produce a wide range of autoantibodies, including antibodies against DNA ( Andrews et al, 1978 ), nucleosomes ( Amoura et al, 1994 ), RNA polymerase ( Stetler et al, 1985 ), cardiolipins ( Gharavi et al, 1989 ), nucleolins ( Hirata et al, 2000 ), phospholipids ( Greenwood et al, 2002 ) and brain antigens ( Moore et al, 1994 ). The pathogenicity of certain autoantibodies in the MRL/ lpr mouse has been called into question.…”

Onset of autoimmune glomerulonephritis derived from the telomeric region of MRL-chromosome 1 is associated with the male sex hormone in mice

“…12 In a recent study, it was confirmed that the Yaa gene was in fact Toll-like receptor 7 (Tlr7), which is localized on the X chromosome encoding an RNA receptor, and that this gene is duplicated on the Y chromosome in BXSB mice. 13 Studies on MRL-Fas lpr (MRL-lpr) mice have reported varying tendencies of sex differences in pathological diseases: some have suggested that the female mice exhibit higher autoantibody levels and more severe glomerulonephritis than the males, 14,15 while others have reported no sex differences between the mice in this regard. [16][17][18] Therefore, it has been considered that sex-related differences in the pathogenesis of autoimmune diseases are strongly affected not only by gene mutations in the individuals but also by their genetic backgrounds.…”