Tg(Prnp/PRNP*AHQ)EM16Pcg

The 12-kb transgene, derived from the pPrHG "half genomic" vector, contains the promoter and first exon of the mouse prion protein gene (Prnp), mouse exon 2 joined to a chimeric mouse/sheep exon 3, and the 3'-untranslated region (UTR) of the mouse gene. The chimeric exon contains nucleotides (nt) 1-117 of the mouse Prnp coding sequence, encoding amino acids (aa) 1-39, and nt 118-762 of the sheep PRNP coding sequence encoding aa 40-253 of the AHQ prion protein variant, which has alanine, histidine and glutamine at ovine polymorphic codons 136, 154 and 171 (A136H154Q171). This allele, while conferring relative resistance to infection of sheep with classic scrapie, is strongly associated with susceptibility to atypical scrapie. The transgene copy number of homozygous transgenic mice of line EM16 was estimated by Southern blot analysis to be 19 +/- 1. Expression of the chimeric protein in brain homogenates from homozygous transgenic mice of this line, estimated by western blot analysis using enhanced chemiluminescence and autoradiography for visualization and densitometric quantitation, is 8-16-fold that seen in normal ovine brainstem. (J:32214, J:223991)