The natural atypical scrapie phenotype is preserved on experimental transmission and sub-passage in PRNP homologous sheep

However, atypical scrapie isolates have been shown to be infectious experimentally, through intracerebral inoculation in transgenic mice and sheep. The first successful challenge of a sheep with 'field' atypical scrapie from an homologous donor sheep was reported in 2007.This study demonstrates that atypical scrapie has distinct clinical, pathological and biochemical characteristics which are maintained on transmission and sub-passage, and which are distinct from other strains of transmissible spongiform encephalopathies in the same host genotype.Atypical scrapie is consistently transmissible within AHQ homozygous sheep, and the disease phenotype is preserved on sub-passage.Atypical scrapie was first identified in Norwegian sheep in 1998 [1], and has subsequently been identified in many European countries [2] and elsewhere around the world, including North America [3] and the Falkland Islands [4]. Retrospective studies have identified cases predating this initial identification [5,6] and epidemiological studies have indicated that this form of scrapie does not conform to the behaviour of an infectious disease [7]. In many cases, atypical scrapie does not co-exist with classical scrapie (e.g. on individual farms, but also at a national level, such as in Portugal and the Falkland Islands [8]), although some field cases originate from flocks which have also reported classical scrapie, and it has occurred in a closed research flock with endemic classical disease [9]. It has also been reported in a research flock in which detailed biosecurity measures have been maintained, founded with sheep from a country free of classical scrapie [10]. This has led to proposals [2,10,11] that this form of scrapie is in fact a spontaneous disease which may have existed undetected for a long time.Despite lack of evidence for infectivity in the epidemiological data, atypical scrapie isolates have been shown to be infectious experimentally, through intracerebral inoculation into ovinised t