Spontaneous autoimmune skin lesions of MRL/n mice: Autoimmune disease-prone genetic background in relation to fas-defect MRL/lpr mice

The autoimmune-prone MRL/Mp-1pr/1pr (MRL/1pr) mouse is characterized by the 1pr mutation, which is a defect in the Fas antigen, Since Fas mediates apoptosis, this defect results in CD4(-)CD8(-) double negative T-cell proliferation, lupus nephritis, and macroscopic lupus erythematosus-like skin lesions. The control counterpart of MRL/1pr mouse is the MRL/Mp-+/+ (MRL/n) mouse, which lacks the 1pr mutation and is almost normal during the first 6 mo of life, The 1pr) mutation, however, accelerates autoimmune phenomena in MRL/1pr mice, Thus, it is important to investigate autoimmune diseases like systemic lupus erythematosis in relation to the autoimmune disease-prone genetic background of MRL/n mice. We found that skin lesions in aged MRL/n mice had unique characteristics. The first characteristic is spontaneous occurrence, and the second is epidermal cell nuclear immunostaining with IgGs by direct immunofluorescence. The skin lesions in aged MRL/n mice showed milder inflammation than in MRL/1pr mice, A homogeneous pattern of epidermal cell nuclear staining was always associated with nuclear staining in kidney cells and also correlated with the in vitro binding of sera to keratinocytes cultured from newborn MRL/n mice, These results suggest that the skin lesions of aged MRL/n mice are a good model for certain types of cutaneous lupus erythematosus and also can provide new insights into the long-standing controversy whether epidermal cell nuclear staining occurs in vivo.