The pathogen common to all transmissible spongiform encephalopathies (TSEs) is the 'prion', the major or sole component of which is an abnormal glycoprotein (PrPSc). The 'benign' isomer of this protein is normally expressed as cellular prion protein (PrPC), which is converted to its pathological isoform. It is thought that, following oral ingestion, the pathological form of the prion protein (PrPSc) can change the cellular form (PrPC) to a pathological one. TSEs have been studied in higher organisms including primates, rodents, etc, but little is known about TSE pathogenesis in fish and lower vertebrates. However, fish farming is becoming a very important industry, providing high protein nutrition. All farmed fish receive commercial food containing 40-55% protein. Animal proteins may also be present and the occurrence of the pathological protein cannot be excluded.
The objectives of this proposal include the study of the effects produced by oral administration of scrapie and BSE infectious material to trout, sea bream and sea bass. It will include the evaluation of tissue lesions in these fish species resulting from the primary transmission. As well, several tissue homogenate samples from fish challenged with experimental mouse scrapie will be used to evaluate any disease symptoms in recipient mice.
Molecular studies will allow the identification and characterisation of DNA sequences encoding fish PrP and PrP-like proteins as potential targets necessary for the transmission of TSEs in these lower vertebrates. Expression of recombinant mature PrPs from fish species may allow antibody production and the identification of markers for neuropathological disorders.
Progress to Date
Partner 1: Pilot studies indicate that the protocols developed for the TSE pathogenesis studies in sea bream and sea bass are feasible.
Partner 2: Identification and cloning of two zebrafish cDNA sequences encoding two distinct proteins exhibiting similarities to the prion protein (PrP).Protein 1, called PrP-like protein and protein 2, called Shadoo, has been accomplished.
Partner 3: Preliminary studies indicate that some residual infectivity is observed in trout intestine taken one day after oral infectious. Some recipient mice inoculated with brain and spleen of turbot resulted positive for scrapie.
Partner 4: Sequence information on PrP-like genes of Atlantic salmon have been obtained.
ANIMALS, FISHERIES AND AQUACULTURE, HUMAN HEALTH AND WELLBEING
Scientist responsible for the project
Assoc. Prof. THEODOROS SKLAVIADIS
6th Km CHARILAOU - THERMI ROAD Box 361
57001 THERMI - THESSALONIKI
Greece - GR
Phone: +30 2310 997615
Fax: +30 2310 997645
||CENTRE FOR RESEARCH AND TECHNOLOGY - HELLAS / INSTITUTE FOR AGROBIOTECHNOLOGY
||29 November 2002
||2 058 876 €
|Total EC contribution
||1 304 432 €