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The use of PrP transgenic Drosophila to replace and reduce vertebrate hosts in the bioassay of mammalian prion infectivity [version 1; referees: 2 approved]

Published version
Peer-reviewed

Change log

Authors

Thackray, AM 
Andréoletti, O 

Abstract

Prion diseases are fatal neurodegenerative conditions of humans and vertebrate species. The transmissible prion agent is a novel infectious particle composed principally of PrP Sc, an abnormal isomer of the normal host protein PrP C. The only reliable method to detect mammalian prion infectivity is by bioassay, invariably in a vertebrate host. The current prion bioassays typically involve intracerebral or peripheral inoculation of test material into the experimental host and subsequent euthanasia when clinical signs of terminal prion disease become evident. It may be months or years before the onset of clinical disease becomes evident and a pre-determined clinical end-point is reached. Consequently, bioassay of prion infectivity in vertebrate species is cumbersome, time consuming, expensive, and increasingly open to ethical debate because these animals are subjected to terminal neurodegenerative disease. Prions are a significant risk to public health through the potential for zoonotic transmission of animal prion diseases. Attention has focussed on the measurement of prion infectivity in different tissues and blood from prion-infected individuals in order to determine the distribution of infectious prions in diseased hosts. New animal models are required in order to replace or reduce, where possible, the dependency on the use of vertebrate species, including the 'gold standard' mouse prion bioassay, to assess prion infectivity levels. Here we highlight the development of a Drosophila-based prion bioassay, a highly sensitive and rapid invertebrate animal system that can efficiently detect mammalian prions. This novel invertebrate model system will be of considerable interest to biologists who perform prion bioassays as it will promote reduction and replacement in the number of sentient animals currently used for this purpose. This article is a composite of previous methods that provides an overview of the methodology of the model and discusses the experimental data to promote its viability for use instead of more sentient hosts.

Description

Keywords

prion, infectivity, bioassay, invertebrate, Drosophila

Journal Title

F1000Research

Conference Name

Journal ISSN

2046-1402
1759-796X

Volume Title

7

Publisher

F1000 Research Ltd
Sponsorship
National Centre for the Replacement Refinement and Reduction of Animals in Research (NC/R00093X/1)
National Centre for the Replacement Refinement and Reduction of Animals in Research (NC/K000462/1)