, 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( ) and VM( ) congenic mice. In VM( ) mice, a 5.5 kb I fragment hybridized to the PrP cDNA sequence whereas VM( ) congenic mice had a 3.8 kb I fragment. The VM × VM( ) congenic F mice had both the 5.5 kb and the 3.8 kb fragments. The donor mouse strain, C57BL, had the 3.8 kb fragment suggesting that the gene and the gene coding for PrP are linked, and could even be the same gene. Other inbred mice (IM and MB) had the 5.5 kb fragment but so too did some strains (RIII and VL), implying that the I site polymorphism is not functionally involved in the difference between the two alleles. We have mapped the polymorphic I site to the 3′ flanking region of the PrP gene. I and I were also found to show polymorphisms in the inbred mouse strains studied. The apparent RFLP with I may be a result of differences in methylation rather than in sequence.

Keyword(s): RFLP , SAF and Sinc

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