title: Degeneration of skeletal muscle, peripheral nerves, and the central nervous system in transgenic mice overexpressing wild-type prion proteins.
abstract: Prion diseases of humans and animals are known to be caused by infection with prions containing PrPSc or mutation of the prion protein (PrP) gene. During transgenetic studies, we discovered that uninoculated older mice harboring high copy numbers of wild-type (wt) PrP transgenes derived from Syrian hamsters (SHa), sheep (She), and PrP-B mice developed truncal ataxia, hindlimb paralysis, and tremors. These transgenic (Tg) mice exhibited a profound necrotizing myopathy involving skeletal muscle, a demyelinating polyneuropathy, and focal vacuolation of the central nervous system. Development of disease was dependent on transgene dosage. For example, half of all Tg(SHaPrP+/+)7 mice homozygous for the SHaPrP transgene array developed disease by approximately 460 days of age, while no hemizygous Tg(SHaPrP+/o)7 mice became ill before 650 days. The novel neurologic syndrome found in older Tg(wtPrP) mice implies that overexpression of wtPrPC is pathogenic and widens the spectrum of prion diseases.
authors.affiliation: Department of Neurology, University of California, San Francisco 94143.
authors.forename: D
authors.initials: D
authors.lastname: Westaway
authors.forename: S J
authors.initials: SJ
authors.lastname: DeArmond
authors.forename: J
authors.initials: J
authors.lastname: Cayetano-Canlas
authors.forename: D
authors.initials: D
authors.lastname: Groth
authors.forename: D
authors.initials: D
authors.lastname: Foster
authors.forename: S L
authors.initials: SL
authors.lastname: Yang
authors.forename: M
authors.initials: M
authors.lastname: Torchia
authors.forename: G A
authors.initials: GA
authors.lastname: Carlson
authors.forename: S B
authors.initials: SB
authors.lastname: Prusiner
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000473:pathology; D001921:Brain / Q000473:pathology*; D006224:Cricetinae; D003711:Demyelinating Diseases / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000032:analysis; D005911:Gliosis / Q000473:pathology; D006720:Homozygote; D008297:Male; D008647:Mesocricetus; D051379:Mice; D008822:Mice, Transgenic; D009132:Muscles / Q000473:pathology*; D009928:Organ Specificity; D010375:Pedigree; D010525:Peripheral Nerves / Q000473:pathology*; D017096:Prion Diseases / Q000235:genetics* / Q000473:pathology* / Q000503:physiopathology; D011328:Prions / Q000235:genetics* / Q000472:pathogenicity; D012756:Sheep
chemical_list: D005904:Glial Fibrillary Acidic Protein; D011328:Prions