MRL/1 and BXSB male mice have a systemic lupus erythematosus (SLE)-like disease similar to but more acute than that occurring in NZB X W mice. The common elements of lymphoid hyperplasia, B-cell hyperactivity, autoantibodies, circulating immune complex (IC), complement consumption, IC glomerulonephritis with gp70 deposition, and thymic atrophy were found in all three kinds of SLE mice. On the basis of these common elements, SLE seen in these mice can be considered a single disease in the same sense that human SLE is one disease. The differences in the SLE expressed in the different mice are no greater than those found in an unselected series of humans with SLE. However, the significant quantitative and qualitative variations in abnormal immunologic expression suggest that different constellations of factors, genetic and/or pathophysiologic, may operate in the three murine strains and that each constellation is capable of leading, via its particular abnormal immunologic consequences, to the activation of common immunopathologic effector mechanisms that cause quite similar SLE-like syndromes. From an experimental point of view, the availability of several inbred murine strains of commonplace histocompatibility types that express an SLE-like syndrome makes possible innumerable manipulations which should help to elucidate the nature and cause(s) of this disorder.

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New Zealand black (NZB) mice and their Fx hybrids (NZB x W) spontaneously develop a disease that closely resembles human systemic lupus erythematosus (SLE) 1 (1, 2). The immunologic abnormalities of this disorder are characterized by the formation of several types of autoantibodies and immune complex (1C) glomerulonephritis (3-5). Endogenous retroviruses and their gene products have been implicated in the pathogenesis of murine SLE (6, 7), partially because of the remarkably high concentrations of the retroviral envelope glycoprotein, gp70, found in sera of NZ mice (6,8,9), and partly because gp70 is deposited in diseased glomeruli along with host immunoglobulins (Ig) and complement and nuclear antigens (4, 6, 7). Like NZB and NZB x W mice, the newly developed murine strains, MRL/1 and BXSB, also spontaneously develop an SLE-like disease and although their serum levels of gp70 are not as high as those of NZ mice, gp70 is deposited in diseased glomeruli (10). Considering that serum gp70 may form gp70-anti-gp70 ICs and, subsequently, deposit in glomerular lesions, we compared the four strains of SLE-prone mice to several immunologically normal murine strains with comparable levels of serum gp70 for the presence of circulating ICs. For this purpose, the molecular size of serum gp70 was determined by sucrose density gradient analysis, and the amount of rapidly sedimeriting gp70 which was found bound to Ig was quantitated throughout the course of disease.We found that sera from all SLE mice contained a heavy form of gp70 complexed to Ig, and that these complexes appeared with the onset of renal disease and persisted throughout its course. By contrast, the normal strains of mice with comparable serum gp70 levels did not have heavy gp70.

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Endogenous expression of the murine leukemia virus (MuLV) genome has been studied in a number of strains of mice. Expression of the major envelope glycoprotein, gp70, is restricted to certain anatomical sites and cell types, prominent among which are lymphoid and epithelial cells. On a quantitative basis, the major site of gp70 expression is the male genital tract. During development, gp70 first appears in the hematopoietic liver of 14-day-old embryos and by day 18, it is already expressed at anatomical sites similar to those of the adult. In toto, these results show that control of expression of the MuLV genome in adult and developing mice is linked to differentiation.