Absence of proteinase K‐resistant PrP in Korean Holstein cattle carrying potential bovine spongiform encephalopathy‐related E211K somatic mutation

Abstract

Bovine spongiform encephalopathy (BSE) is a kind of prion disease caused by proteinase K‐resistant prion protein (PrPSc) in cattle. Although BSE has been reported worldwide, BSE‐infected cases have never been reported in Korea. In a previous study, we identified BSE‐related somatic mutation E211K in 3 Korean Holstein cattle. In Korea, the BSE surveillance system has been established. However, several genetic factors have not been controlled simultaneously thus far. In the present study, we performed enhanced surveillance of prion disease‐related factors in Korean cattle, including Holstein cattle and Hanwoo (Korean native cattle), which is widely raised for meat. We investigated the germline mutation E211K at codon 211 of the PRNP gene and analysed genotype, allele and haplotype frequencies of the 23‐ and 12‐bp insertion/deletion polymorphisms of the PRNP gene using direct DNA sequencing. In addition, we investigated linkage disequilibrium (LD) and compared haplotype distributions of polymorphisms among cattle breeds. Furthermore, we carried out BSE diagnosis in the medulla oblongata (MO) of Korean cattle including 3 Korean Holstein cattle carrying somatic mutation E211K using Western blotting analysis. We did not find the E211K mutation in the PRNP gene in any of the Korean cattle and found significantly different genotype, allele and haplotype distributions of the 23‐ and 12‐bp insertion/deletion polymorphisms of the PRNP gene in male Holstein compared with male Hanwoo, female Hanwoo and total Hanwoo. In addition, only male Holstein showed weak LD between 23‐ and 12‐bp insertion/deletion polymorphisms. Furthermore, the PrPSc bands were not detected in all Korean cattle tested. To the best of our knowledge, the enhanced surveillance system of BSE was conducted for the first time in Korean cattle.

The First Report of Polymorphisms and Genetic Characteristics of the Shadow of Prion Protein (SPRN) in Prion Disease-Resistant Animal, Chickens

“…Prion diseases are fatal and infectious neurodegenerative disorders caused by the misfolded toxic form of prion protein (PrP Sc ) originating from a benign form of prion protein (PrP C ). Although the conversion process of PrP C to PrP Sc is still unclear, several factors that play a pivotal role in the conversion have been identified thus far (1)(2)(3)(4)(5). Among these factors, previous studies have reported that the shadow of prion protein (Sho) interacts with prion protein (PrP) and accelerates the conversion of PrP C to PrP Sc (6).…”

In‐depth examination of PrP Sc in Holstein cattle carrying the E211K somatic mutation of the bovine prion protein gene ( PRNP )

“…The animals did not show any clinical and histopathological features. Detailed information regarding the tested animals was presented in a previous study (Y. C. Kim et al., 2022; Won et al., 2020). The Tg( PRNP )1896Pcg/FVB mice carrying bovine PRNP gene (GenBank ID: AJ298878) were obtained from the Jackson laboratory.…”

“…In the present study, we carried out an in-depth examination on PrP Sc by using enzyme immunoassay (EIA), RT-QuIC and PMCA in three Holstein cattle carrying the E211K somatic mutation of the bovine PRNP gene. Kim et al, 2022;Won et al, 2020). The Tg(PRNP)1896Pcg/FVB mice carrying bovine PRNP gene (GenBank ID: AJ298878) were obtained from the Jackson laboratory.…”

“…Since the bovine E211K PRNP mutation was considered a potential BSE‐related pathogenic mutation, it was notable. However, the proteinase K‐resistant PrP Sc band was not detected in any of the tested animals using western blot analysis (Kim Y.C., Won, Jeong & Jeong, 2022). The detection limit for western blot analysis was shown to be as little as 4 ng of protein.…”

Association Study of the M132L Single Nucleotide Polymorphism With Susceptibility to Chronic Wasting Disease in Korean Elk: A Meta-Analysis

“…Prion diseases are infectious brain proteinopathies caused by a pathogenic form of prion protein (PrP Sc ) converted from an endogenous form of prion protein (PrP C ) and are classified into several types in a wide range of mammalian hosts: Creutzfeldt-Jakob disease (CJD), fatal familial insomnia (FFI) and Gerstmann-Sträussler-Scheinker syndrome (GSS) in humans; scrapie in sheep and goats; bovine spongiform encephalopathy (BSE) in cattle; and chronic wasting disease (CWD) in the Cervidae family (1)(2)(3)(4)(5)(6)(7). After CWD was first reported in mule deer in the USA in the 1967, CWD has been reported globally, including in North America, South Korea and Scandinavia, in variable cervid species, such as white-tailed deer, elk, moose, red deer and reindeer (8)(9)(10)(11).…”