A transgenic construct was engineered to contain murine Prnp lacking sequence encoding amino acids 32 through 93. Sequence, including that encoding the amino-terminal signal sequence, necassary for proper transport to the endoplasmic reticulum and properprocessing was left intact. Transgenic expression was verified by Western blot analysis. Only after treatment with PNGase did the transgenic protein migrate a distance corresponding to the deletion, indicating in vivo glycosylation. A carboxy terminal cleavage product was also detected. The murine Prnp promoter drove expression of similar transgenes (lines 11 and 12) the forebrain and cerebellum. Transgenic transcript was identified in all layers of the cerebellum except for Purkinje cells. Nuclear injections were made in zygotes carrying Prnptm1Cwe.