The Journal of Veterinary Medical Science the Presence of Disease-associated Prion Protein in Skeletal Muscle of Cattle 3 Infected with Classical Bovine Spongiform Encephalopathy 4 5

The aim of this study was to investigate the presence of disease-associated 20 prion protein (PrP Sc) in the skeletal muscle of cattle infected with classical bovine 21 spongiform encephalopathy (C-BSE). The study was carried out systematically in 12 22 different muscle samples from 43 (3 field and 40 experimental) cases of C-BSE; 23 however, muscle spindles were not available in many of these cases. Therefore, analysis 24 became restricted to a total of 31 muscles in 23 cattle. Even after this restriction, low 25 levels of PrP Sc were detected in the muscle spindles of the masseter, intercostal, triceps 26 brachii, psoas major, quadriceps femoris and semitendinosus muscles from 3 field and 6 27 experimental clinical-stage cases. The present data indicate that small amounts of PrP Sc 28 are detectable by immunohistochemistry in the skeletal muscles of animals terminally 29 affected with C-BSE. 30 31 KEY WORDS: BSE, muscle spindle, prion, skeletal muscle 32 33 3 Classical bovine spongiform encephalopathy (C-BSE) in cattle is a fatal 34 neurodegenerative disorder belonging to a group of transmissible spongiform 35 encephalopathies (TSEs). C-BSE was first identified in the United Kingdom in 1986 36 [18] and subsequently spread to Europe, North America and Japan. The disease is 37 characterized by spongiform changes and the accumulation of a disease-associated 38 abnormal form of prion protein (PrP Sc) in the central nervous system. PrP Sc is 39 commonly accepted as the pathological agent of TSEs and may be a post-translationally 40 modified form of a normal cellular prion protein (PrP C) [14].The C-BSE agent is 41 transmissible to various mammalian species. For example, the variant form of 42 Creutzfeldt-Jakob disease (CJD) in humans likely resulted from consumption of 43 C-BSE-contaminated foodstuff [19]; therefore, issues regarding C-BSE and variant CJD 44 have increased public health concerns regarding the safety of meat products used for 45 food. 46 A low level of infectivity was identified in the semitendinosus muscle of a 47 clinically C-BSE-affected field case through a mouse bioassay using highly sensitive 48 transgenic mice overexpressing bovine PrP C [3]. Recently, PrP Sc deposition in skeletal 49 muscles of cattle experimentally infected with atypical BSE was visualized by 50 immunohistochemistry (IHC) [8, 15]. The detailed topological distribution of PrP Sc in 51 the muscular tissues of C-BSE-infected cattle, however, remains unclear [2]. Here, we 52 describe the localization of immunolabeled PrP Sc in the skeletal muscles …