title: Ataxia in prion protein (PrP)-deficient mice is associated with upregulation of the novel PrP-like protein doppel.
abstract: The novel locus Prnd is 16 kb downstream of the mouse prion protein (PrP) gene Prnp and encodes a 179 residue PrP-like protein designated doppel (Dpl). Prnd generates major transcripts of 1.7 and 2.7 kb as well as some unusual chimeric transcripts generated by intergenic splicing with Prnp. Like PrP, Dpl mRNA is expressed during embryogenesis but, in contrast to PrP, it is expressed minimally in the CNS. Unexpectedly, Dpl is upregulated in the CNS of two PrP-deficient (Prnp(0/0)) lines of mice, both of which develop late-onset ataxia, suggesting that Dpl may provoke neurodegeneration. Dpl is the first PrP-like protein to be described in mammals, and since Dpl seems to cause neurodegeneration similar to PrP, the linked expression of the Prnp and Prnd genes may play a previously unrecognized role in the pathogenesis of prion diseases or other illnesses.
authors.affiliation: Institute for Neurodegenerative Diseases, Departments of Neurology.
authors.forename: R C
authors.initials: RC
authors.lastname: Moore
authors.forename: I Y
authors.initials: IY
authors.lastname: Lee
authors.forename: G L
authors.initials: GL
authors.lastname: Silverman
authors.forename: P M
authors.initials: PM
authors.lastname: Harrison
authors.forename: R
authors.initials: R
authors.lastname: Strome
authors.forename: C
authors.initials: C
authors.lastname: Heinrich
authors.forename: A
authors.initials: A
authors.lastname: Karunaratne
authors.forename: S H
authors.initials: SH
authors.lastname: Pasternak
authors.forename: M A
authors.initials: MA
authors.lastname: Chishti
authors.forename: Y
authors.initials: Y
authors.lastname: Liang
authors.forename: P
authors.initials: P
authors.lastname: Mastrangelo
authors.forename: K
authors.initials: K
authors.lastname: Wang
authors.forename: A F
authors.initials: AF
authors.lastname: Smit
authors.forename: S
authors.initials: S
authors.lastname: Katamine
authors.forename: G A
authors.initials: GA
authors.lastname: Carlson
authors.forename: F E
authors.initials: FE
authors.lastname: Cohen
authors.forename: S B
authors.initials: SB
authors.lastname: Prusiner
authors.forename: D W
authors.initials: DW
authors.lastname: Melton
authors.forename: P
authors.initials: P
authors.lastname: Tremblay
authors.forename: L E
authors.initials: LE
authors.lastname: Hood
authors.forename: D
authors.initials: D
authors.lastname: Westaway
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D001259:Ataxia / Q000235:genetics*; D001483:Base Sequence; D002460:Cell Line; D002490:Central Nervous System / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D003001:Cloning, Molecular; D004622:Embryo, Mammalian / Q000378:metabolism; D058851:GPI-Linked Proteins; D017353:Gene Deletion; D006031:Glycosylation; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D011328:Prions / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D011689:Purkinje Cells / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D016415:Sequence Alignment; D020040:Trans-Splicing / Q000235:genetics; D015854:Up-Regulation
chemical_list: D058851:GPI-Linked Proteins; D011328:Prions; C122036:Prnd protein, mouse; D012333:RNA, Messenger