title: Resistance to classical scrapie in experimentally challenged goats carrying mutation K222 of the prion protein gene.
abstract: Susceptibility of sheep to scrapie, a transmissible spongiform encephalopathy of small ruminants, is strongly influenced by polymorphisms of the prion protein gene (PRNP). Breeding programs have been implemented to increase scrapie resistance in sheep populations; though desirable, a similar approach has not yet been applied in goats. European studies have now suggested that several polymorphisms can modulate scrapie susceptibility in goats: in particular, PRNP variant K222 has been associated with resistance in case-control studies in Italy, France and Greece. In this study we investigated the resistance conferred by this variant using a natural Italian goat scrapie isolate to intracerebrally challenge five goats carrying genotype Q/Q 222 (wild type) and five goats carrying genotype Q/K 222. By the end of the study, all five Q/Q 222 goats had died of scrapie after a mean incubation period of 19 months; one of the five Q/K 222 goats died after 24 months, while the other four were alive and apparently healthy up to the end of the study at 4.5 years post-challenge. All five of these animals were found to be scrapie negative. Statistical analysis showed that the probability of survival of the Q/K 222 goats versus the Q/Q 222 goats was significantly higher (p = 0.002). Our study shows that PRNP gene mutation K222 is strongly associated with resistance to classical scrapie also in experimental conditions, making it a potentially positive target for selection in the frame of breeding programs for resistance to classical scrapie in goats.
authors.affiliation: CEA, Italian Reference Laboratory for TSEs, Neuroscienze - Istituto Zooprofilattico Sperimentale del Piemonte, Liguria e Valle d'Aosta, Via Bologna 148, 10154 Torino, Italy. pierluigi.acutis@izsto.it.
authors.forename: Pier Luigi
authors.initials: PL
authors.lastname: Acutis
authors.forename: Francesca
authors.initials: F
authors.lastname: Martucci
authors.forename: Antonio
authors.initials: A
authors.lastname: D'Angelo
authors.forename: Simone
authors.initials: S
authors.lastname: Peletto
authors.forename: Silvia
authors.initials: S
authors.lastname: Colussi
authors.forename: Cristiana
authors.initials: C
authors.lastname: Maurella
authors.forename: Chiara
authors.initials: C
authors.lastname: Porcario
authors.forename: Barbara
authors.initials: B
authors.lastname: Iulini
authors.forename: Maria
authors.initials: M
authors.lastname: Mazza
authors.forename: Luana
authors.initials: L
authors.lastname: Dell'atti
authors.forename: Fabio
authors.initials: F
authors.lastname: Zuccon
authors.forename: Cristiano
authors.initials: C
authors.lastname: Corona
authors.forename: Nicola
authors.initials: N
authors.lastname: Martinelli
authors.forename: Cristina
authors.initials: C
authors.lastname: Casalone
authors.forename: Maria
authors.initials: M
authors.lastname: Caramelli
authors.forename: Guerino
authors.initials: G
authors.lastname: Lombardi
mesh_terms: D000818:Animals; D004591:Electrophoresis, Polyacrylamide Gel / Q000662:veterinary; D005260:Female; D015511:Goat Diseases / Q000209:etiology / Q000235:genetics* / Q000473:pathology / Q000635:transmission; D006041:Goats; D007558:Italy; D008163:Luminescent Measurements / Q000662:veterinary; D008297:Male; D009154:Mutation; D016133:Polymerase Chain Reaction / Q000662:veterinary; D011110:Polymorphism, Genetic; D011328:Prions / Q000235:genetics* / Q000378:metabolism; D012608:Scrapie / Q000209:etiology / Q000235:genetics* / Q000473:pathology / Q000635:transmission
chemical_list: D011328:Prions