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

Es. Jenkins et Rd. Combes, The welfare problems associated with using transgenic mice to bioassay forbovine spongiform encephalopathy, ANIM WELFAR, 8(4), 1999, pp. 421-431
Citations number
Categorie Soggetti
Animal Sciences
Journal title
ISSN journal
0962-7286 → ACNP
Year of publication
421 - 431
SICI code
Prion diseases are fatal neurodegenerative disorders, epitomized by the rec ent bovine spongiform encephalopathy (BSE) epidemic in cattle and the emerg ence of a novel variant of Creutzfeldt-Jacob disease (vCJD) in humans. In p rion disease, the agent of infection is believed to be composed of proteina ceous particles, termed prions, which are converted from a normal isoform i nto a pathogenic isoform during pathogenesis. A bioassay to detect pathogen ic prions of BSE in bovine products consumed by humans was unattainable unt il the development of transgenic mice, due to the significantly lower susce ptibility of wild-type mice to BSE. Transgenic mice have now been generated which express the bovine prion protein and are susceptible to BSE. Followi ng an intracerebral injection with brain homogenate of BSE-infected cattle, transgenic mice develop numerous clinical signs of prion disease, includin g truncal ataxia (inability to coordinate the torso's muscular activity), i ncreased tone of the tail generalized tremor; and lack of a forelimb extens or response. In this study, the ethical score system devised by Porter (1992) was applie d to the BSE bioassay, as a tool for identifying welfare issues affecting a nimals used in the bioassay. We acknowledge that there are limitations to t he use of the information arising from the application of the Porter scorin g scheme for assessing the justification to proceed with any animal experim ent; notwithstanding these problems, however, our application of the Porter model to the BSE bioassay enabled us to identify potential targets for ref inement: pain involved, duration of distress and the duration of the experi ment. This was despite lenient scoring for the duration of distress and pai n experienced by the mice, and optimal scoring for the quality of animal ca re. The targets identified for refinement are discussed in relation to the method of inoculation, the duration of the bioassay, and the duration of th e clinical phase. with the objective of exploring ways of reducing the seve rity, of the bioassay.