PARADOXICAL SHORTENING OF SCRAPIE INCUBATION TIMES BY EXPRESSION OF PRION PROTEIN TRANSGENES DERIVED FROM LONG INCUBATION PERIOD MICE

Prolonged incubation times for experimental scrapie in I/LnJ mice are dictated by a dominant gene linked to the prion protein gene (Prn-p). Transgenic mice were analyzed to discriminate between an effect of the I/LnJ Prn-p(b) allele and a distinct incubation time locus designated Prn-i. Paradoxically, 4 independent Prn-p(b) transgenic mouse lines had scrapie incubation times shorter than nontransgenic controls, instead of the anticipated prolonged incubation periods. Aberrant or overexpression of the Prn-p(b) transgenes may dictate abbreviated incubation times, masking genuine Prn-p/Prn-i congruence; alternatively, a discrete Prn-i gene lies adjacent to Prn-p.