Caprine PRNP polymorphisms N146S and Q222K are associated with proteolytic cleavage of PrP(C)

Expression of the cellular prion protein (PrP(C)) is crucial for the development of prion diseases. Amino acid changes in PrP(C) or a reduced amount of PrP(C) may modulate disease resistance. The relative abundance of C1, a natural α-cleavage fragment of PrP(C), was previously found to be associated with a resistant PRNP genotype in sheep. Goats are another small ruminant where classical scrapie susceptibility is under strong genetic control. In this study, we assessed PrP(C) in goats for the existence of similar associations between PrP(C) fragments and genotype. Brain tissue homogenates from scrapie-free goats with wild type PRNP or polymorphisms (I142M, H143R, N146S, or Q222K) were deglycosylated prior to immunoblot for assessment of the relative abundance of the C1 fragment of PrP(C). The presence of K(222) or S(146) alleles demonstrated significantly different relative levels of C1 compared to that observed in wild type goats, which suggests that the genotype association with C1 is neither unique to sheep nor exclusive to the ovine Q171R dimorphism. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12711-021-00646-x.