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ARS Home » Pacific West Area » Dubois, Idaho » Range Sheep Production Efficiency Research » Research » Publications at this Location » Publication #199642

Title: Effects of nutrition and genotype on prion protein (PrP-c) gene expression and localization in the fetal and maternal sheep placenta.

item EVONIUK, J.M.
item JOHNSON, M.L.
item Taylor, Joshua - Bret
item O'Rourke, Katherine
item REDMER, D.A.

Submitted to: Placenta
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 2/9/2008
Publication Date: 5/1/2008
Citation: Evoniuk, J., Johnson, M., Borowicz, P., Caton, J.S., Vonnahme, K., Reynolds, J., Taylor, J.B., Stoltenow, C., Orourke, K.I., Redmer, D. 2008. Effects of Nutrition and Genotype on Prion Protein (PrPC) Gene Expression in the Fetal and Maternal Sheep Placenta. Placenta. 29(5):422-428.

Interpretive Summary: Scrapie is a fatal disease of sheep, apparently spread by contamination of pastures and lambing barns by placentas containing the infectious agent. The factors controlling accumulation of the infectious agent in the placenta include the genetics of the fetus, although other contributing factors have not been examined. The infectious agent is associated with an abnormal form (PrP-Sc) of a normal protein (PrP-c). In experimental rodent models, increasing amounts of PrP-c result in increased susceptibility to scrapie. Because maternal nutrition is an important factor in placental development, this study investigated the effects of fetal genotype and maternal nutrition on the amount of PrP-c in the placenta. They demonstrated small but significant increase in PrP-c levels in ewes with a nutritionally restricted diet but no changes associated with fetal genotype. If PrP-c levels are an indicator of relative susceptibility in sheep, this study suggests that flock management practices may play a role in scrapie transmission.

Technical Abstract: Scrapie is the prototype transmissible spongiform encephalopathy, or prion disease, of domestic livestock. The disease appears to be transmitted most readily by post-parturient ewes and the presence of the marker protein PrP-Sc in the shed fetal cotyledon suggests that contamination of the lambing pens by placentas of infected ewes contributes to spread of the disease. Relative scrapie susceptibility is associated with naturally occurring polymorphisms in the gene (PRNP) encoding the normal isoform (PrP-c) of the marker protein. PrP-c expression is necessary for infection and rodent models suggest that overexpression of the gene is associated with increased susceptibility. In this study, the investigators examined the effect of genotype and maternal nutrition on the level of PRNP mRNA and PrP-c in the ovine placenta. PrP-c expression was primarily localized to the fetal cotyledon, primarily the trophoblast cells, the site of PrP-Sc accumulation in the infected ewe. There were no genotype effects on PrPC protein expression however cotyledonary PrPC mRNA expression was greater (P < 0.02) when codon 136 was homozygous for alanine (1.41 ± 0.08; n = 40) compared to heterozygous tissue (0.86 ± 0.07). PrP-c levels were reduced in ewes receiving adequate nutrition through pregnancy compared to those with nutritional restriction. This finding suggests that husbandry may play an accessory role in scrapie susceptibility.