Submitted to: Journal of Clinical Pathology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/12/2003
Publication Date: 7/20/2004
Citation: Caplazi, P., Orourke, K.I., Baszler, T.V. 2004. Resistance to scrapie in prp arr/arq heterozygous sheep is not caused by preferential allelic usage. Journal of Clinical Pathology. 57:647-650. Interpretive Summary: Scrapie is a fatal disease of sheep. Although the disease is caused by a transmissible agent, probably spread by contact with infected placentas at the time of lambing, susceptibility to the disease is genetically related. Scrapie control in the US includes genetic selection for resistant animals. The molecular basis for genetic resistance is unknown. In this study, the relative amount of the messenger RNA encoding the form of the prion protein associated with susceptibility was compared to the amount of messenger RNA encoding the resistant form. The study demonstrated that there was no significant different in the amounts of messenger RNA for each protein. Additional studies examining other molecular mechanisms for genetic control of scrapie are underway.
Technical Abstract: Scrapie is a transmissible spongiform encephalopathy of sheep and goats. The transmissible agent appears to involve a protease resistant isoform of a normal ovine protein. The disorder is transmitted during lambing, presumably through contact with the transmissible agent shed in placenta. Although the disorder is transmissible under field conditions, susceptibility is genetically controlled. In the US, the predominant strain of scrapie affects sheep homozygous for glutamine at residue 171. Sheep homozygous for the alternative allele encoding arginine 171 are protected from disease. Heterozygous sheep are also protected although the mechanism for disease resistance is not known. In this study, the investigators examine the hypothesis that resistance in heterozygous sheep is due to down-regulation of mRNA encoding the glutamine171 allele in the presence of mRNA encoding the arginine171 allele. Polymerase chain reaction and cloning of cDNA showed no difference in mRNA expression of the two alleles in heterozygous sheep. Alternative mechanisms for genetic protection from scrapie are under investigation.