Alteration of the biological and biochemical characteristics of bovine spongiform encephalopathy prions during interspecies transmission in transgenic mice models

Abstract

In the interspecies transmission of prions, the species barrier influences the susceptibility of the host. Bovine spongiform encephalopathy (BSE) prions affect a wide range of host species but do not affect hamsters. In order to study this species barrier, this study analysed the transmissibility of BSE prions to several lines of transgenic (Tg) mice, including those expressing mouse and hamster chimeric prion proteins (MH2M and MHM2 mice). BSE prions were transmitted to tga20, MHM2 and ICR mice, and the incubation period was approximately 400 days. Thus, these mice were classified as 'susceptible mice'. However, BSE prions were not transmitted to MH2M and TgHaNSE mice, and these mice were classified as 'resistant mice'. After the BSE prions were passaged once in wild-type mice, they could be transmitted to resistant mice. The characteristics of the accumulated abnormal isoform of PrP (PrP Sc ) in susceptible and resistant mice were determined using Western blotting. A BSE-like glycoform pattern of PrP Sc was detected in all of the susceptible mice using two different antibodies that recognized either the N-or the C-terminal end of the 27-30 kDa protease-resistant fragment of PrP (PrP 27-30 ) as the epitope. In contrast, proteinase digestion followed by deglycosylation analysis showed that, in addition to PrP 27-30 , truncated PrP Sc fragments existed in resistant mice. These mixed PrP Sc fragments may have resulted from the adaptation of resistant mice to BSE prions.

Alteration of the Chronic Wasting Disease Species Barrier byIn VitroPrion Amplification

“…However, the latter difference may be due to the lack of PrP C expression by Purkinje cells in this transgenic mouse strain (7,27). The differences in neuropathological features between CWD-infected voles and Tg(CerPrP)1536 mice are consistent with the alterations in strain properties sometimes observed upon transspecies passage of CWD and other TSEs (26,35,39).…”

Strain-Specific Barriers against Bovine Prions in Hamsters

“…The lack of transmissibility of the classical BSE agent from cattle to hamsters and its efficient transmission after a first passage in C57BL/6 wild-type mice are consistent with the results of previous studies (11,20,21). Hamsters were also susceptible to the SSBP/1 isolate from ovine transgenic TgOvPrP4 mice, consistent with the known susceptibility of hamsters to some scrapie sources (14).…”

“…The initial isolation of two biologically different prion strains, associated with distinct PrP properties, in transmissible mink encephalopathy (TME) was first achieved in hamsters (5). Surprisingly, bioassay studies in hamsters after challenge with the C-type BSE agent from cattle showed that it was inefficient (11,21). This was attributed to the existence of a so-called "species barrier," a concept based on the observation that the transmission of prion diseases between different species is typically far less efficient than within species (10).…”

Scientific Opinion on a request for a review of a scientific publication concerning the zoonotic potential of ovine scrapie prions

“…However, the conclusion that transgenic mice overexpressing PrP C lead to a considerable reduction of the incubation time is also a point still open to debate: indeed, while this is true for a number of mouse and hamster strains, this statement seems not to be true in all cases. As an example, the incubation time of BSE in tg mice which over-express mouse PrP (tga20) is similar if not longer than in wild type mice (Yokoyama et al, 2009). …”