Scrapie strain transmission studies in ovine PrP transgenic mice reveal dissimilar susceptibility

Abstract

The Tg(OvPrP4) mouse line, expressing the sheep prion protein, is a sensitive model crucial for the identification of the bovine spongiform encephalopathy agent possibly present in natural sheep spongiform encephalopathies. It was also previously demonstrated as susceptible to infection with natural scrapie isolates from sheep harbouring various genotypes. The performance of this new transgenic mouse line in scrapie strain characterization was further assessed by intracranial inoculation of five groups of Tg(OvPrP4) mice with brain homogenate of the wild type mouse-adapted scrapie strains, C506M3, 22A, 79A, 87V, or Chandler. The Tg(OvPrP4) mice were susceptible to the scrapie agent transmitted using mouse-adapted scrapie strains but not equivalently. Strains 87V and Chandler were most readily transmissible followed by 79A and C506M3. Strain 22A was the least transmissible. Clinical signs, survival data, spongiosis, and PrP(sc) distribution were also reported. These various data demonstrate the possibility of distinguishing between scrapie strains. Our findings are discussed with regard to agent strain and host factors and already demonstrate the dissimilar susceptibilities of Tg(OvPrP4) mice to the different murine strains studied, thus, reinforcing their potential use in strain typing studies.

Rabbits are not resistant to prion infection

“…Animals can be both extremely susceptible to the majority of prion diseases or strains yet remain resistant to others on first passage (21). Therefore, it would be unwise to assume that a species generally resistant to TSEs would represent a minor risk to human health, as new TSEs and strains are continually being detected.…”

State-of-the-art technologies, current opinions and developments, and novel findings: news from the field of histochemistry and cell biology

“…A number of recent studies have used immunolabeling methods in investigating diVerent aspects of the distribution of the cellular prion protein and of consequences of infections with the pathologic prion protein in various species, tissues, and using a wide variety of methods (e.g., Debeer et al 2003;Lezmi et al 2003;Amselgruber et al 2006;Bencsik et al 2006Bencsik et al , 2007Dorban et al 2007;Miyazawa et al 2007). The limits of detection in immunolabeling are particularly critical when this technique is used for localization of the abnormal prion protein (PrPsc) for diagnostic purposes.…”

“…The limits of detection in immunolabeling are particularly critical when this technique is used for localization of the abnormal prion protein (PrPsc) for diagnostic purposes. Bencsik et al (2006Bencsik et al ( , 2007 recently developed a new ampliWcation method in the immunohistochemical detection of PrPsc using streptomycin sulphate. Now, the authors applied this method to acquire new insights into early sequential PrPsc accumulation in scrapie infected mouse brain (Bencsik et al 2008).…”

Insights into Mechanisms of Transmission and Pathogenesis from Transgenic Mouse Models of Prion Diseases

“…Ovine Tg mice have been shown to be a useful tool for discriminating scrapie strains [137] and in particular for differentiating BSE in sheep from natural scrapie isolates [128, 132, 138]. Tg mouse models are also at the forefront of characterizing a relatively newly-emerging ‘atypical’ scrapie strain [139] related to so-called Nor98 cases first identified in Norwegian sheep.…”