title: A mouse prion protein transgene rescues mice deficient for the prion protein gene from purkinje cell degeneration and demyelination.
abstract: Disruption of both alleles of the prion protein gene, Prnp, renders mice resistant to prions; in a Prnp o/o line reported by some of us, mice progressively developed ataxia and Purkinje cell loss. Here we report torpedo-like axonal swellings associated with residual Purkinje cells in Prnp o/o mice, and we demonstrate abnormal myelination in the spinal cord and peripheral nerves in mice from two independently established Prnp o/o lines. Mice were successfully rescued from both demyelination and Purkinje cell degeneration by introduction of a transgene encoding wild-type mouse cellular prion protein. These findings suggest that cellular prion protein expression may be necessary to maintain the integrity of the nervous system.
authors.affiliation: Department of Bacteriology, Nagasaki University School of Medicine, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Nishida
authors.forename: P
authors.initials: P
authors.lastname: Tremblay
authors.forename: T
authors.initials: T
authors.lastname: Sugimoto
authors.forename: K
authors.initials: K
authors.lastname: Shigematsu
authors.forename: S
authors.initials: S
authors.lastname: Shirabe
authors.forename: C
authors.initials: C
authors.lastname: Petromilli
authors.forename: S P
authors.initials: SP
authors.lastname: Erpel
authors.forename: R
authors.initials: R
authors.lastname: Nakaoke
authors.forename: R
authors.initials: R
authors.lastname: Atarashi
authors.forename: T
authors.initials: T
authors.lastname: Houtani
authors.forename: M
authors.initials: M
authors.lastname: Torchia
authors.forename: S
authors.initials: S
authors.lastname: Sakaguchi
authors.forename: S J
authors.initials: SJ
authors.lastname: DeArmond
authors.forename: S B
authors.initials: SB
authors.lastname: Prusiner
authors.forename: S
authors.initials: S
authors.lastname: Katamine
mesh_terms: D020413:3' Untranslated Regions; D000483:Alleles; D000818:Animals; D001921:Brain / Q000473:pathology*; D006224:Cricetinae; D003711:Demyelinating Diseases / Q000235:genetics* / Q000503:physiopathology / Q000517:prevention & control; D005091:Exons; D007438:Introns; D008647:Mesocricetus; D051379:Mice; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D009043:Motor Activity; D010525:Peripheral Nerves / Q000473:pathology; D011328:Prions / Q000235:genetics* / Q000502:physiology*; D011597:Psychomotor Performance; D011689:Purkinje Cells / Q000473:pathology*; D013116:Spinal Cord / Q000473:pathology; D014617:Vacuoles / Q000473:pathology
chemical_list: D020413:3' Untranslated Regions; D011328:Prions