Genetic studies of autoimmunity and retrovirus expression in crosses of New Zealand black mice I. Xenotropic virus.

Abstract

Type C RNA viruses (retroviruses) have been implicated in the autoimmune disease of New Zealand Black (NZB) 1 mice (1, 2). However, the evidence for this is only circumstantial because the retroviruses isolated from NZB mice are xenotropic in host range; this prohibits a direct test of their pathogenicity in mice by, for example, inoculation of filtrates (3, 4). Nevertheless, the relationship between autoimmunization and xenotropic viruses c&n be ascertained by genetic tests because the genes of these agents are an integral part of cellular chromosomes (5) and their expression in NZB mice is governed by two autosomal dominant genes (6, 7). In this paper we describe results of genetic experiments designed to test the hypothesis that expression of xenotropic virus is required for the development of autoimmune disease. The following paper (8) deals with the relationship between autoimmune disease in NZB mice and expression of the major envelope glycoprotein of the virus, gp70. Materials and MethodsMice. NZB, SWR, C57BL/6, B10.A, and AKR mice were obtained from The Jackson Laboratory, Bar Harbor, Maine. Reciprocal crosses were made to produce FI and backcross progeny mice. Because the maternal direction of the cross did not affect the results, all data for a given cross were pooled and presented by a single nomenclature: F~ for (SWR × NZB)F~; (F~ × SWR) for backcross to SWR, and (F~ x NZB) for backcross to NZB. The mice were 11-24 mo old when tested.Retrovirus Assays XI~.NOTROPIC VIRUS. Spleen cell suspensions were prepared and serially diluted as described previously (6, 7, 9). They were assayed by cocultivation on monolayers of the feline 81 cell line

Lymphocyte antigens in systemic lupus erythematosus: studies with heterologous antisera.

“…Presently there is no evidence that the lymphocyte membrane antigen(s) detected with the extensively absorbed anti-SLE antisera described here have any relationship to virus or cell surface determinants related to any viral genome (37)(38)(39)(40). Considerably more work will be necessary before such a possibility can be resolved.…”

Immuno- and genetic therapy in autoimmune diseases

“…63 In contrast to NZW, which can develop mild nephritis late in life, the SWR1 mouse is completely healthy and has a normal life span. Clinically, the SNF1 mouse is similar to BWF1 mice, with most females dead by 10-12 months and with a 50% mortality rate at 6 months of age with an immune glomerulonephritis that is mediated primarily by IgG2b antibodies to DNA.…”

Genetic studies in NZB mice

“…Investigators have shown that the NZB xenotropic virus production is inherited as a dominant trait and is independent of the development of other autoimmune traits (Datta and Schwartz, 1976;Datta et al, 1978). Since virus production seems to be a dominant trait, the (NZB X DBA) F| mice should have high titers of virus, yet they did not have chromosomal abnormalities.…”