Conservation des "prions" chez les Vertébrés

Abstract

Conservation of the prion proteins in Vertebrates The word prion (which stands for proteinaceous infectious agent) has originally been coined in 1982 to name the presumed, and unconventional, etiological agent of the transmissible spongiform encephalopathies, a group of neurodegenerative diseases which affect the central nervous system of humans and other mammals. Since that time, this word's meaning has widened enormously, so that it is now used to designate a vast group of divergent proteins, sometimes even in unicellular organisms like the baker's yeast. This paper is aimed at reviewing the problem of the existence of "prions", or PrP genes in non-mammalian vertebrates. At present, definite PrP genes have been found in several bird species, and in one turtle. However, the proteins encoded by these genes are divergent from the mammalian ones. In fishes, there is presently no evidence for a PrP. Our group has looked for PrP gene(s) in trout and medaka, by various means (screen of a trout expression library with an anti-PrP antibody, of a cDNA medaka brain library with mouse and sheep DNA probes, and by PCR) and never got a positive result. Searches in fish -especially zebrafish-databases were unable to detect a sequence with similarities to known prions. It can be concluded from these negative results that an eventual fish PrP gene is probably very divergent from those characterised in mammals; and that it would be extremely unlikely to share the pathological properties of these latter molecules. In a more general perspective, it appears that the problem of the nomenclature of the so-called "prion" proteins needs an update and a clarification.