title: 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.
abstract: 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 (PrP(Sc)) accumulation in the placenta. To test whether other PRNP polymorphisms are associated with a lack of placental PrP(Sc) deposition, we carried out a study on 26 naturally and 11 experimentally scrapie-affected ewes with or without clinical signs. PrP(Sc) was detected in the placenta of ARQ/ARQ(wild type) fetuses by Western blot and immunohistochemical analysis, but not in ARQN(176)/ARQK(176) or, as expected, ARQ/ARR samples. Furthermore, three of four AL(141)RQ/AF(141)RQ placentas were also PrP(Sc) negative, suggesting that the dimorphism at codon 141 may also mediate placental deposition of PrP(Sc). 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 PrP(Sc).
authors.affiliation: Istituto Zooprofilattico Sperimentale della Sardegna, 07100 Sassari, Italy.
authors.forename: Cinzia
authors.initials: C
authors.lastname: Santucciu
authors.forename: Caterina
authors.initials: C
authors.lastname: Maestrale
authors.forename: Laura
authors.initials: L
authors.lastname: Madau
authors.forename: Sonia
authors.initials: S
authors.lastname: Attene
authors.forename: Maria Giovanna
authors.initials: MG
authors.lastname: Cancedda
authors.forename: Franca
authors.initials: F
authors.lastname: Demontis
authors.forename: Maria Giovanna
authors.initials: MG
authors.lastname: Tilocca
authors.forename: Mariangela
authors.initials: M
authors.lastname: Saba
authors.forename: Simona
authors.initials: S
authors.lastname: Macciocu
authors.forename: Antonello
authors.initials: A
authors.lastname: Carta
authors.forename: Ciriaco
authors.initials: C
authors.lastname: Ligios
mesh_terms: D019943:Amino Acid Substitution; D000818:Animals; D003062:Codon / Q000235:genetics; D005260:Female; D005838:Genotype; D010920:Placenta / Q000378:metabolism*; D020641:Polymorphism, Single Nucleotide; D018620:PrPSc Proteins / Q000235:genetics* / Q000378:metabolism*; D011247:Pregnancy; D011248:Pregnancy Complications / Q000235:genetics / Q000378:metabolism; D012608:Scrapie / Q000150:complications / Q000235:genetics* / Q000378:metabolism* / Q000635:transmission; D012756:Sheep
chemical_list: D003062:Codon; D018620:PrPSc Proteins