Abstract
Natural scrapie transmission from infected ewes to their lambs is thought to occur by the oral route around the time of birth. However the hypothesis that scrapie transmission can also occur before birth (in utero) is not currently favoured by most researchers. As scrapie is an opportunistic infection with multiple infection routes likely to be functional in sheep, definitive evidence for or against transmission from ewe to her developing fetus has been difficult to achieve. In addition the very early literature on maternal transmission of scrapie in sheep was compromised by lack of knowledge of the role of the PRNP (prion protein) gene in control of susceptibility to scrapie. In this study we experimentally infected pregnant ewes of known PRNP genotype with a distinctive scrapie strain (SSBP/1) and looked for evidence of transmission of SSBP/1 to the offspring. The sheep were from the NPU Cheviot flock, which has endemic natural scrapie from which SSBP/1 can be differentiated on the basis of histology, genetics of disease incidence and strain typing bioassay in mice. We used embryo transfer techniques to allow sheep fetuses of scrapie-susceptible PRNP genotypes to develop in a range of scrapie-resistant and susceptible recipient mothers and challenged the recipients with SSBP/1. Scrapie clinical disease, caused by both natural scrapie and SSBP/1, occurred in the progeny but evidence (including mouse strain typing) of SSBP/1 infection was found only in lambs born to fully susceptible recipient mothers. Progeny were not protected from transmission of natural scrapie or SSBP/1 by washing of embryos to International Embryo Transfer Society standards or by caesarean derivation and complete separation from their birth mothers. Our results strongly suggest that pre-natal (in utero) transmission of scrapie may have occurred in these sheep.
Highlights
Scrapie is one of the transmissible spongiform encephalopathies (TSE) or prion diseases
Susceptibility to TSEs in sheep is controlled by alleles of the gene encoding PrP, known as PRNP, and much is understood about the pathogenesis and strain targeting of different PRNP genotypes, the transmission of natural scrapie from sheep to sheep is not fully understood
The three rams all died of causes unrelated to scrapie at ages of around 2,000 days and over 1,000 days after being used for artificial insemination
Summary
Scrapie is one of the transmissible spongiform encephalopathies (TSE) or prion diseases It occurs naturally in sheep and goats but can be transmitted by experimental inoculation. Susceptibility to TSEs in sheep is controlled by alleles of the gene encoding PrP, known as PRNP, and much is understood about the pathogenesis and strain targeting of different PRNP genotypes, the transmission of natural scrapie from sheep to sheep is not fully understood. More recently the interaction between sheep PRNP genotype and incidence of natural and experimental scrapie was elucidated [2,3] and as scrapie is not a genetic disease [4,5] the perception of maternal transmission is realised to be at least partly the result of inheritance of PRNP alleles specifying susceptibility to a prevalent infection. One in Scotland, UK [1] and the other in the US [6], supported the idea of mother to offspring transmission of scrapie in sheep
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