The Absence of Prion-Like Infectivity in Mice expressing Prion Protein-Like Protein

Abstract

Cellular prion protein, PrP^C, undergoes pathogenic structural conversion into the proteinase K (PK)-resistant isoform, PrP^Sc, to constitute a nucleic acid-free infectious agent, so called a prion. To determine whether a recently identified PrP-like protein, named PrPLP/Dpl, could also be transformed to a prion-like protein, we intracerebrally inoculated a mouse-adapted Fukuoka-1 prion into Ngsk and Zrch I mice either homozygously (Prnp^0/0) or heterozygously (Prnp^0/+) devoid of PrP^C. Only the former expressed PrPLP/Dpl ectopically in the brains, particularly in neurons. Ngsk Prnp^0/+ and Zrch I Prnp^0/+ mice similarly developed the disease. The diseased Ngsk Prnp0/+ mice transmitted the disease to the mice expressing PrP^C but not to the mice expressing PrPLP/Dpl, showing abundant accumulation of PrP^Sc but not PK-resistant PrPLP/Dpl in the brains. Moreover, the inoculated Ngsk Prnp^0/0 mice neither developed the disease nor produced any infectivity transmissible to PrPLP/Dpl-expressing mice. These results indicate that PrPLP/Dpl have no potential to undergo pathogenic conversion to form a prion-like infectious particle.