Linkage of prion protein and scrapie incubation time genes

A single gene ( Prn-i) that affects scrapie incubation period in mice has been identified. I LnJ mice have a very long incubation period after inoculation of scrapie prions (200–385 days) and NZW LacJ mice have a short one (113 ± 2.8 days). (NZW × I Ln )F1 hybrid mice had incubation times of 223 ± 2.8 days indicating longer incubation times were dominant. Incubation periods in the backcross progeny of ( NZW LacJ × I LnJ )F1 × NZW LacJ segregated into two groups (64 mice, 130 ± 1.1 d; 66 mice, 195 ± 1.9 d) indicating single gene control. NZW LacJ and 20 other inbred strains have the Prn-p a allele which is identified as a 3.8 kb Xbal fragment using a hamster PrP (prion protein) cDNA probe. I LnJ and three other Prn-p b mouse strains have a 5.5 kb Xbal restriction fragment. Analysis of DNA from 66 backcross mice indicated Prn-i is tightly linked to Prn-p, the structural gene for PrP.