Ataxia in prion protein (PrP)-deficient mice is associated with upregulation of the novel PrP-like protein doppel

• Published in: Journal of molecular biology Vol. 292; no. 4; pp. 797 - 817
• Main Authors: Moore, Richard C, Lee, Inyoul Y, Silverman, Gregory L, Harrison, Paul M, Strome, Robert, Heinrich, Cornelia, Karunaratne, Amila, Pasternak, Stephen H, Chishti, M.Azhar, Liang, Yan, Mastrangelo, Peter, Wang, Kai, Smit, Arian F.A, Katamine, Shigeru, Carlson, George A, Cohen, Fred E, Prusiner, Stanley B, Melton, David W, Tremblay, Patrick, Hood, Leroy E, Westaway, David
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01-10-1999
• Subjects: Amino Acid Motifs; Amino Acid Sequence; Animals; ataxia; Ataxia - genetics; Base Sequence; Cell Line; Central Nervous System - cytology; Central Nervous System - metabolism; Central Nervous System - pathology; Cloning, Molecular; doppel protein; Embryo, Mammalian - metabolism; Gene Deletion; Glycosylation; GPI-Linked Proteins; Male; Mice; Mice, Inbred BALB C; Mice, Transgenic; Molecular Sequence Data; neurodegeneration; prion; Prions - chemistry; Prions - genetics; Prions - metabolism; Prions - physiology; Prnd gene; prnp gene; PrP; Purkinje Cells - metabolism; Purkinje Cells - pathology; Purkinje neuron; RNA, Messenger - analysis; RNA, Messenger - genetics; Sequence Alignment; Trans-Splicing - genetics; Up-Regulation; Dpl; GPI; ORF; Purkinje neuron; neurodegeneration; CMV; PrP; DMEM; Tg; ataxia; PGK; FBS; RACE; prion; CLD; HBSS; CJD; wt
• ISSN: 0022-2836; 1089-8638
• DOI: 10.1006/jmbi.1999.3108

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.