Characterization of a prion protein (PrP) gene from rabbit; a species with apparent resistance to infection by prions.
The prion protein gene (PrP) encodes a cellular protein of unknown function. A conformational isoform of this protein is involved in the neurodegenerative prion diseases. To facilitate the identification of structurally and antigenically important regions within the PrP molecule, the rabbit PrP open reading frame (ORF) was cloned and characterised. There is 82-87% identity at the nucleotide sequence level and 88-93% identity at the amino acid (aa) sequence level, between the rabbit gene and PrP sequences of other mammals. The rabbit gene shares structural and organisational features common to all known PrP genes signifying that it is the rabbit PrP gene. Comparison of the rabbit PrP aa sequence with PrP aa sequences from different species revealed several potential epitopes. Two anti-ovine PrP peptide Ab raised in rabbits, 168-92 and 98-92, confirmed that two separate cross-reacting epitopes segregate with single aa differences between rabbit and sheep PrP at positions 43 and 99 of the rabbit PrP polypeptide. The presence of these epitopes correlates with the species recognition patterns of previously published Ab. The usefulness of the rabbit PrP gene sequence in predicting antigenic regions within the PrP proteins of various species is illustrated. The structure of the rabbit PrP protein in relation to rabbits apparent resistance to infection by prions is discussed.
Loftus
B
B
Zoology Department, University College, Dublin, Ireland.
Rogers
M
M
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D003001:Cloning, Molecular; D003429:Cross Reactions; D004247:DNA; D018985:Epitopes, B-Lymphocyte / Q000032:analysis; D007113:Immunity, Innate / Q000235:genetics; D008969:Molecular Sequence Data; D016366:Open Reading Frames; D010455:Peptides / Q000235:genetics; D011328:Prions / Q000737:chemistry / Q000235:genetics* / Q000276:immunology; D014176:Protein Biosynthesis; D011487:Protein Conformation; D011817:Rabbits; D015183:Restriction Mapping; D012608:Scrapie / Q000276:immunology*; D013045:Species Specificity
D018985:Epitopes, B-Lymphocyte; D010455:Peptides; D011328:Prions; D004247:DNA