A genomic fragment encompassing the entire coding region contained within exon 3 as well as approximately 1 kb of sequence 5' to exon 3 was replaced with a PGK-HPRT cassette. The deleted upstream sequence included the exon 3 splice acceptor site. RT-PCR analysis of RNA obtained from homozygous mutant brain tissue showed increased levels of chimeric transcript consisting of Prnp and Prnd sequence relative to wild-type samples. (J:42407)