"Natural" RT6-1 and RT6-2 "knock-out" mice.

We have screened different mouse strains-including strains with enhanced susceptibility for autoimmune diseases-for deviations of Rt6 gene expression by RT-PCR. Most strains expressed varying amounts of Rt6-1 and Rt6-2. NZW mice, however, do not show any detectable Rt6-2 gene transcripts. BxSB mice show a near complete absence of Rt6-1 gene transcripts. Southern blot and sequence analyses revealed that NZW mice have suffered a deletion of the Rt6.2 gene while the Rt6-1 gene of BxSB mice has been inactivated by a premature stop codon. Thus, these mouse strains represent natural Rt6-2 and Rt6-1 single-gene 'knock-out's, respectively. Since the NZW mouse does not show any gross immunological abnormalities, loss of the Rt6-2 gene by itself is not associated with any obvious immunological phenotype. However, crosses between NZW and certain other mouse strains, e.g. (NZW x NWB)F1 and (NZW x SB)F1 animals, develop a systemic autoimmune disease reminiscent of human lupus erythematosus. Moreover, the BxSB mouse strain is considered to be an independent model for the same disease. It will be of interest to determine whether these spontaneous Rt6 gene defects constitute part of the polygenetic contribution to autoimmune disease in these animals.