Spongiform encephalopathy (BSE), susceptibility
Gene: PRNP
Transmission: Unknown
Mutation: Substitution, PRNP gene; c.631 G>A, p.(Glu211Lys), chromosome 13.
Breed: Cattle, ruminants, horse, wild mammals, humans.
Medical system: Neurological
Age of onset of symptoms: Long incubation time (2.5 – 8 years).
Spongiform encephalopathy, also known as Bovine Spongiform Encephalitis (BSE) or Mad Cow disease, is a type of fatal neurodegenerative disease seen in cattle. BSE is similar to scrapies seen in sheep and goats, chronic wasting disease seen in deer, and Creutzfeld-Jakob disease (CJD) seen in humans. These diseases are known as prion diseases and are caused by a misfolded natural protein, PrP, coded for by the PRNP gene. The natural protein is a widely expressed cell membrane glycoprotein whose function is unknown. Misfolding of the PrP protein by inappropriate glycosylation and disulfide bonding results in a scrapie-Prp protein that can “recruit” normal PrP proteins to misfold, making the scrapie-PrP protein an infectious agent. Notably, the normal PrP and the scrapie-Prp proteins can have the same amino acid primary structure and be different only in secondary conformation. The production of scrapie-PrP proteins results in amyloid accumulation in brain tissues and the neurological symptoms associated with the disease. These symptoms include progressive signs of ataxia, tremors, incoordination, weight loss, decreased production, aggression and eventually recumbency and death. There is no treatment. Diagnosis is post-mortem.
Two types of BSE are described in cattle, the classical type and the atypical type. Classical BSE occurred in the United Kingdom during the 1980s and 1990s, as a result of cattle consuming prion contaminated feed. Both horizontal and vertical transmission in cattle was seen. Notably, classical BSE was transmissible to humans who had consumed contaminated bovine products, resulting in a variation of Creutzfeld-Jakob disease. The atypical type of BSE appears sporadically in cattle at an estimated frequency of 1 case in 1 million animals. Familial cases of CJD are seen in humans and are often associated with a germline mutation (E210K) in the PrP protein sequence. The equivalent mutation in the bovine PrP protein sequence (E211K) has been identified in somatic tissues from one animal diagnosed with atypical BSE and from several animals not exhibiting symptoms of BSE. The susceptibility or resistance to BSE conferred by this mutation requires further investigation.
Bovine spongiform encephalopathy has been known to cause disease in humans. Appropriate measures and reporting should be exercised.
References:
OMIA link: [0944-9913]
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Lestari TD, Khairullah AR, Utama S, et al. (2025) Bovine spongiform encephalopathy: A review of current knowledge and challenges. Open Vet J 15:54-68. [40092198]
Kim YC, Park KJ, Hwang JY, et al. (2022) In-depth examination of PrP Sc in Holstein cattle carrying the E211K somatic mutation of the bovine prion protein gene (PRNP). Transbound Emerg Dis 69:e356-e361. [pm/34470082]
Won S-Y, Kim Y-C, Jeong B-H. (2020) First report of the potential bovine spongiform encephalopathy (BSE)-related somatic mutation E211K of the prion protein gene (PRNP) in cattle. Int J Mol Sci 21(12):4246. [pm/32549191]
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Contributed by: Aurélie Moreau and Sofia Pinero-Tabah, Class of 2029, Faculté de médecine vétérinaire, Université de Montréal. (Translation DWS)