Expression of an endogenous retroviral transcript is associated with murine lupus

We have been investigating whether murine lupus is associated with endogenous type C retroviral expression. We used Northern blot analyses and oligonucleotide probes, which are able to distinguish the envelope genes of the xenotropic and mink cell focus-forming (MCF) classes of type C retroviruses. Xenotropic expression in the spleen varied markedly among inbred mouse strains; although all strains expressed a 1.8-kb transcript, only one-half expressed one or more larger transcripts (8.4, 7.2, and/or 3.0 kb). Autoimmune disease did not correlate with expression of any of the xenotropic transcripts. Xenotropic and MCF transcripts were expressed independently among the mouse strains studied. Splenic RNA from all strains contained 7.2-, 3.0-, and 1.8-kb MCF transcripts. Some strains also expressed 8.4-kb MCF splenic RNA. There was a strong association between murine lupus and expression of 8.4-kb MCF transcripts: 6 of 6 lupus-prone strains, but only 2 of 11 nonautoimmune strains, had detectable 8.4-kb MCF RNA. The xid and Yaa mutations had minimal effects on expression of 8.4-kb MCF-related transcripts, despite their major and opposite effects on disease. Moreover, New Zealand black mice highly expressed this RNA from day 1 of life, before disease development. The data suggest that expression of 8.4-kb MCF endogenous retroviral transcripts is a primary feature of murine lupus and is not secondary to disease expression.