title: Structure and polymorphism of the mouse prion protein gene.
abstract: Missense mutations in the prion protein (PrP) gene, overexpression of the cellular isoform of PrP (PrPC), and infection with prions containing the scrapie isoform of PrP (PrPSc) all cause neurodegenerative disease. To understand better the physiology and expression of PrPC, we retrieved mouse PrP gene (Prn-p) yeast artificial chromosome (YAC), cosmid, phage, and cDNA clones. Physical mapping positions Prn-p approximately 300 kb from ecotropic virus integration site number 4 (Evi-4), compatible with failure to detect recombination between Prn-p and Evi-4 in genetic crosses. The Prn-pa allele encompasses three exons, with exons 1 and 2 encoding the mRNA 5' untranslated region. Exon 2 has no equivalent in the Syrian hamster and human PrP genes. The Prn-pb gene shares this intron/exon structure but harbors an approximately 6-kb deletion within intron 2. While the Prn-pb open reading frame encodes two amino acid substitutions linked to prolonged scrapie incubation periods, a deletion of intron 2 sequences also characterizes inbred strains such as RIII/S and MOLF/Ei with shorter incubation periods, making a relationship between intron 2 size and scrapie pathogenesis unlikely. The promoter regions of a and b Prn-p alleles include consensus Sp1 and AP-1 sites, as well as other conserved motifs which may represent binding sites for as yet unidentified transcription factors.
authors.affiliation: Department of Neurology, University of California, San Francisco 94143.
authors.forename: D
authors.initials: D
authors.lastname: Westaway
authors.forename: C
authors.initials: C
authors.lastname: Cooper
authors.forename: S
authors.initials: S
authors.lastname: Turner
authors.forename: M
authors.initials: M
authors.lastname: Da Costa
authors.forename: G A
authors.initials: GA
authors.lastname: Carlson
authors.forename: S B
authors.initials: SB
authors.lastname: Prusiner
mesh_terms: D000818:Animals; D001483:Base Sequence; D001921:Brain / Q000378:metabolism*; D003001:Cloning, Molecular; D006224:Cricetinae; D004247:DNA / Q000235:genetics; D017931:DNA Primers; D004251:DNA Transposable Elements; D018076:DNA, Complementary / Q000378:metabolism; D005091:Exons; D006801:Humans; D007438:Introns; D008647:Mesocricetus; D051379:Mice; D008810:Mice, Inbred C57BL / Q000235:genetics; D008815:Mice, Inbred Strains / Q000235:genetics*; D008969:Molecular Sequence Data; D016366:Open Reading Frames; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D018620:PrPSc Proteins; D011328:Prions / Q000235:genetics*; D011401:Promoter Regions, Genetic; D017384:Sequence Deletion; D012689:Sequence Homology, Nucleic Acid; D012756:Sheep
chemical_list: D017931:DNA Primers; D004251:DNA Transposable Elements; D018076:DNA, Complementary; D018620:PrPSc Proteins; D011328:Prions; D004247:DNA