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