Linkage of the scrapie-associated fibril protein (PrP) gene and Sinc using congenic mice and restriction fragment length polymorphism analysis.

Sinc, with two alleles p7 and s7, is the major gene determining the incubation period of all strains of scrapie in mice. The major protein (PrP) of scrapie-associated fibrils is encoded by a cellular gene and we have used a cDNA copy of the hamster PrP mRNA to carry out restriction fragment length polymorphism (RFLP) analysis of different inbred mouse strains including VM(Sincp7) and VM(Sincs7) congenic mice. In VM(Sincp7) mice, a 5.5 kb XbaI fragment hybridized to the PrP cDNA sequence whereas VM(Sincs7) congenic mice had a 3.8 kb XbaI fragment. The VM X VM(Sincs7) congenic F1 mice had both the 5.5 kb and the 3.8 kb fragments. The Sincs7 donor mouse strain, C57BL, had the 3.8 kb fragment suggesting that the Sinc gene and the gene coding for PrP are linked, and could even be the same gene. Other Sincp7 inbred mice (IM and MB) had the 5.5 kb fragment but so too did some Sincs7 strains (RIII and VL), implying that the XbaI site polymorphism is not functionally involved in the difference between the two Sinc alleles. We have mapped the polymorphic XbaI site to the 3' flanking region of the PrP gene. TaqI and HhaI were also found to show polymorphisms in the inbred mouse strains studied. The apparent RFLP with HhaI may be a result of differences in methylation rather than in sequence.