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Title: PRPSC ACCUMULATION IN FETAL COTYLEDONS OF SCRAPIE-RESISTANT LAMBS IS INFLUENCED BY FETUS LOCATION IN THE UTERUS

Author
item Alverson, Janet
item O'Rourke, Katherine
item BASZLER, TIMOTHY - WSU

Submitted to: Journal of General Virology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/22/2005
Publication Date: 4/3/2006
Citation: Alverson, J., O'Rourke, K.I., Baszler, T.V. 2006. PrPSc accumulation in fetal cotyledons of scrapie-resistant lambs is influenced by fetus location in the uterus. Journal of General Virology. 87:1035-1041.

Interpretive Summary: We examined fetal tissue from placentas of scrapie infected ewes that gave birth to multiple lambs for the causative agent of scrapie, PrP-Sc. We found that some fetuses of genotypes thought to be resistant to scrapie will accumulate PrP-Sc when they have been positioned next to a fetus of a susceptible genotype that is positive for PrP-Sc during gestation in the uterus. Additionally, we have shown that a product specific to males can be found in the fetal tissue of female fetuses when they have been positioned next to male fetuses during gestation in the uterus. This suggests some sharing of fetal blood between tissues of fetuses that are positioned directly next to each other during gestation in the uterus.

Technical Abstract: Placentas from scrapie infected ewes have been shown to accumulate PrP-Sc when the genotype of the fetus is of a susceptible genotype (VRQ/VRQ, ARQ/VRQ, or ARQ/ARQ). Cotyledons from fetuses of genotypes ARR/ARR, ARQ/ ARR and ARQ/ VRR have previously been shown to be resistant to PrP-Sc accumulation. Using ewes from a naturally infected scrapie flock, we examined cotyledons from fetuses of multiple births of different genotypes. PrP-Sc was detected in fetal cotyledons of genotype ARQ/ARQ, but not in cotyledons from their dizygotic twin of genotype ARQ/ARR. This confirms earlier reports of single fetuses of these genotypes, but is the first description of such a finding in twin fetuses, one of each genotype. We have also shown that cotyledons from sibling fetuses of genotypes ARQ/VRQ and ARQ/ARQ have different patterns of PrP-Sc accumulation depending on whether the dam is of genotype ARQ/ARQ or ARQ/VRQ. Additionally, we have shown that cotyledons from fetuses with resistant genotypes are weakly positive for PrP-Sc when they have shared the same pregnant uterine horn with a fetus of a susceptible genotype with cotyledons positive for the detection of PrP-Sc. We have also shown a PCR product for the Sry gene, a product specific to males, in cotyledons from a female fetus sharing a uterine horn with a male fetus. This suggests some sharing of fetal blood between cotyledons in the same uterine horn prior to parturition.