The welfare problems associated with using transgenic mice to bioassay for bovine spongiform encephalopathy

Prion diseases are fatal neurodegenerative disorders, epitomized by the the recent bovine spongiform encephalopathy (BSE) epidemic in cattle and the emergence of a novel variant of Creutzfeldt-Jacob disease (vCJD) in humans. In prion disease, the agent of infection is believed to be composed of proteinaceous particles, termed prions, which are converted from a normal isoform into a pathogenic isoform during pathogenesis. A bioassay to detect pathogenic prions of BSE in bovine products consumed by humans was unattainable until the development of transgenic mice, due to the significantly lower susceptibility of wild-type mice to BSE. Transgenic mice have now been generated which express the bovine prion protein and are susceptible to BSE. Following an intracerebral injection with brain homogenate of BSE-infected cattle, transgenic mice develop numerous clinical signs of prion disease, including truncal ataxia (inability to coordinate the torso's muscular activity), increased tone of the tail, generalized tremor, and lack of a forelimb extensor response. In this study, the ethical score system devised by Porter (1992) was applied to the BSE bioassay as a tool for identifying welfare issues affecting animals used in the bioassay. We acknowledge that there are limitations to the use of the information arising from the application of the Porter scoring scheme for assessing the justification to proceed with any animal experiment; notwithstanding these problems, however, our application of the Porter model to the BSE bioassay enabled us to identify potential targets for refinement: pain involved, duration of distress and the duration of the experiment. This was despite lenient scoring for the duration of distress and pain experienced by the mice, and optimal scoring for the quality of animal care. The targets identified for refinement are discussed in relation to the method of inoculation, the duration of the bioassay, and the duration of the clinical phase, with the objective of exploring ways of reducing the severity of the bioassay.