Generation of Prnd−/− and Prnp−/−/Prnd−/− mouse lines by gene targeting. a, Prnd; b, Prnp/Prnd. The structure of the Prnp and Prnd loci, targeting constructs, and targeted loci are shown schematically. Exons for each gene are indicated: filled boxes, coding regions; shaded boxes, untranslated regions. In the targeting constructs the positive (HPRT) and negative (HSV-TK) selectable markers are indicated. The locations of PCR primers, probes, and restriction fragments used to identify targeted clones are shown. Restriction sites: B, BamHI; E, EcoRI; P, PstI; S, ScaI; X, XhoI.