Association of N176K and L141F dimorphisms of the PRNP gene with lack of pathological prion protein deposition in placentas of naturally and experimentally scrapie-affected ARQ/ARQ sheep.

The placenta is important in the horizontal transmission of the aetiological agent in scrapie-affected sheep. It has been demonstrated that the placentas of fetuses carrying the dimorphism Q171R of the PRNP gene is resistant to pathological prion protein (PrPSc) accumulation in the placenta. To test whether other PRNP polymorphisms are associated with a lack of placental PrPSc deposition, we carried out a study on 26 naturally and 11 experimentally scrapie-affected ewes with or without clinical signs. PrPSc was detected in the placenta of ARQ/ARQwild type fetuses by Western blot and immunohistochemical analysis, but not in ARQN176/ARQK176 or, as expected, ARQ/ARR samples. Furthermore, three of four AL141RQ/AF141RQ placentas were also PrPSc negative, suggesting that the dimorphism at codon 141 may also mediate placental deposition of PrPSc. This finding demonstrates for the first time that fetal PRNP polymorphisms, other than those at codon 171, are associated with the lack of placental deposition of PrPSc.