Genetic, histochemical and biochemical studies on goat TSE cases from Cyprus.

Scrapie and bovine spongiform encephalopathy (BSE) are transmissible spongiform encephalopathies (TSE's) affecting sheep and goats. Susceptibility of goats to scrapie is influenced by polymorphisms of the prion protein gene (PRNP) of the host. Five polymorphisms are associated with reduced susceptibility to TSE's.

Fish models in prion biology: underwater issues.

Transmissible spongiform encephalopathies (TSEs), otherwise known as prion disorders, are fatal diseases causing neurodegeneration in a wide range of mammalian hosts, including humans. The causative agents - prions - are thought to be composed of a rogue isoform of the endogenous prion protein (PrP). Beyond these and other basic concepts, fundamental questions in prion biology remain unanswered, such as the physiological function of PrP, the molecular mechanisms underlying prion pathogenesis, and the origin of prions.

Evaluation of the possible transmission of BSE and scrapie to gilthead sea bream (Sparus aurata).

In transmissible spongiform encephalopathies (TSEs), a group of fatal neurodegenerative disorders affecting many species, the key event in disease pathogenesis is the accumulation of an abnormal conformational isoform (PrP(Sc)) of the host-encoded cellular prion protein (PrP(C)). While the precise mechanism of the PrP(C) to PrP(Sc) conversion is not understood, it is clear that host PrP(C) expression is a prerequisite for effective infectious prion propagation. Although there have been many studies on TSEs in mammalian species, little is known about TSE pathogenesis in fish.

Design and validation of a high-throughput assay to detect codon 146 polymorphisms in the caprine prion protein gene.

In sheep, scrapie susceptibility is so strongly associated with single nucleotide polymorphisms (SNPs) in the gene encoding the prion protein (PrP) that this linkage constitutes the basis for selective breeding strategies directed toward controlling the disease. For goats, in contrast, the association between scrapie susceptibility/resistance and variations in the PrP gene is far weaker, with only a few identified SNPs showing an influence on scrapie susceptibility. A recent survey of PrP genotypes in Cypriot goats, however, revealed the existence of a robust association between polymorphisms at codon 146 of the caprine PrP gene and resistance/susceptibility to natural scrapie.

State-of-the-art review of goat TSE in the European Union, with special emphasis on PRNP genetics and epidemiology.

Scrapie is a fatal, neurodegenerative disease of sheep and goats. It is also the earliest known member in the family of diseases classified as transmissible spongiform encephalopathies (TSE) or prion diseases, which includes Creutzfeldt-Jakob disease in humans, bovine spongiform encephalopathy (BSE), and chronic wasting disease in cervids. The recent revelation of naturally occurring BSE in a goat has brought the issue of TSE in goats to the attention of the public.

Interactions of the antizyme AtoC with regulatory elements of the Escherichia coli atoDAEB operon.

AtoC has a dual function as both an antizyme, the posttranslational inhibitor of polyamine biosynthetic enzymes, and the transcriptional regulator of genes involved in short-chain fatty acid catabolism (the atoDAEB operon). We have previously shown that AtoC is the response regulator of the AtoS-AtoC two-component signal transduction system that activates atoDAEB when Escherichia coli is exposed to acetoacetate. Here, we show that the same cis elements control both promoter inducibility and AtoC binding.

Molecular characterization of a cDNA from the gilthead sea bream (Sparus aurata) encoding a fish prion protein.

We have identified and characterized a cDNA from the brain tissue of the highly commercial marine fish species, the gilthead sea bream (Sparus aurata), which encodes a 496 amino acid residue protein sharing the organizational and structural features of the mammalian prion proteins. Tissue mRNA expression analyses revealed the presence of this transcript in various tissues of the gilthead sea bream including the brain, the spleen, and the heart. Sequence comparison and phylogenetic analysis showed the gilthead sea bream protein to be the homologue of one of the long form prion proteins identified from the model fish species Takifugu rubripes and Danio rerio.

Involvement of the AtoS-AtoC signal transduction system in poly-(R)-3-hydroxybutyrate biosynthesis in Escherichia coli.

The AtoS-AtoC signal transduction system in E. coli, which induces the atoDAEB operon for the growth of E. coli in short-chain fatty acids, can positively modulate the levels of poly-(R)-3-hydroxybutyrate (cPHB) biosynthesis, a biopolymer with many physiological roles in E.

Disparate evolution of prion protein domains and the distinct origin of Doppel- and prion-related loci revealed by fish-to-mammal comparisons.

Prions result from the misfolding and selective accumulation of the host-encoded prion protein (PrP) in the brain. Despite intensive research on mammalian models, basic questions about the biological role of PrP and the evolutionary origin of prion disease remain unanswered. Following our previous identification of novel fish PrP homologues, here we generated new fish PrP sequences and performed genomic analysis to demonstrate the existence of two homologous PrP loci in bony fish, which display extensive molecular variation and are highly expressed in adult and developing fish brains.

Phosphorylation activity of the response regulator of the two-component signal transduction system AtoS-AtoC in E. coli.

Antizyme, long known to be a non-competitive inhibitor of ornithine decarboxylase, is encoded by the atoC gene in Escherichia coli. The present study reveals another role for AtoC, that of a response regulator of the AtoS-AtoC two component system regulating the expression of the atoDAEB operon upon acetoacetate induction. This operon encodes enzymes involved in short-chain fatty acid catabolism in E.

Prion protein gene polymorphisms in natural goat scrapie.

A total of 51 goats, including seven clinical cases, from the first herd in Greece reported to have scrapie was examined to discern an association between scrapie susceptibility and polymorphisms of the gene encoding the prion protein (PrP). Each animal was evaluated for clinical signs of the disease, histopathological lesions associated with scrapie, the presence of detectable protease-resistant PrP in the brain and PrP genotype. Eleven different PrP genotypes encoding at least five unique predicted mature PrP amino acid sequences were found.