|Hall, S. Mark|
Submitted to: International Winter Meeting of the Swiss Society of Neuropathology
Publication Type: Abstract Only
Publication Acceptance Date: 3/15/2004
Publication Date: 3/24/2004
Citation: Richt, J.A., Kluge, J.P., Alt, D.P., Kunkle, R.A., Hamir, A.N., Czub, S., Davis, A.J., Hall, S.M. 2004. Identification and characterization of the bovine spongiform encephalopathy case diagnosed in the United States [Abstract]. XXth International Winter Meeting of the Swiss Society of Neuropathology. Paper No. 13, p. 29. Interpretive Summary:
Technical Abstract: Bovine spongiform encephalopathy (BSE) is a transmissible spongiform encephalopathy of cattle, first detected in 1986 in the U.K. and subsequently in other countries. BSE may have arisen from feed contaminated with the scrapie agent, which causes a similar disease in sheep and goats, or from a germline mutation in the protein-coding region of the prion protein (PrP) gene of affected cattle. Here, we report on the prion protein polypeptide profile and genotype from the first case of BSE diagnosed in the United States. The six-year old Holstein cow, imported into the State of Washington from Canada in 2001, was nonambulatory at slaughter. The formalin-fixed obex area of the brainstem was found to contain spongiform changes, including vacuolated neurons by histopathology and extensive deposition of the abnormal form of the prion protein, PrPres, by immunohistochemistry (IHC). Western blot analyses and an enzyme-linked immunosorbent assay using brainstem and cerebellum derived from fresh tissue from the suspect animal were consistent with histopathologic and IHC results. The PrPres polypeptide profile from the U.S. BSE case was characterized by (i) a lower molecular mass of the unglycosylated PrPres polypeptide fragment compared to samples from sheep with scrapie and deer with chronic wasting disease, (ii) good immunoreactivity with monoclonal antibody 6H4 directed against the central region of the PrP, but lack of staining with monoclonal antibody P4, which recognizes the protease-resistant N-terminal end of the PrP; and (iii) a glycoform profile with a high proportion of the diglycosylated PrPres isoform. Comparison of the U.S. BSE isolate to the recent Canadian isolate and European BSE isolates revealed similar sized PrPres polypeptide fragments using the anti-PrP antibody 6H4. The PrP gene from the BSE case diagnosed in the U.S. was amplified from both, fresh and formalin-fixed brain material and found to be of bovine origin with a normal, rather unremarkable cattle PrP sequence. This cow had a synonymous polymorphism at codon 192, and both alleles contained the six-copy octapeptide repeat region. We conclude from these studies that (i) the PrPres profile from the first BSE case diagnosed in the U.S. showed similar molecular properties to the typical PrPres pattern described for the earlier Canadian and European BSE isolates, and (ii) a germline mutation in the bovine PrP gene was not evident. This information is consistent with the hypothesis that the U.S. BSE case - similar to the one diagnosed in Canada in May 2003 - was most likely exposed to contaminated feed.