Ataxia in prion protein (PrP)-deficient mice is associated with upregulation of the novel PrP-like protein Doppel
Autor: | Robert Strome, George A. Carlson, David Westaway, Patrick Tremblay, Gregory L. Silverman, Richard C. Moore, Fred E. Cohen, Paul M. Harrison, Stanley B. Prusiner, Leroy Hood, Stephen H. Pasternak, A. Karunaratne, Kai Wang, Inyoul Lee, M A Chishti, D. W. Melton, Yan Liang, Cornelia Heinrich, Peter Mastrangelo, S. Katamine, Arian Fa Smit |
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Předmět: |
Central Nervous System
Male Glycosylation Prions animal diseases Transgene Amino Acid Motifs Molecular Sequence Data Mice Transgenic Biology GPI-Linked Proteins PRNP Cell Line Trans-Splicing Mice Purkinje Cells Downregulation and upregulation Structural Biology medicine Animals Amino Acid Sequence RNA Messenger Cloning Molecular Molecular Biology Gene Peptide sequence Messenger RNA Mice Inbred BALB C Base Sequence Neurodegeneration medicine.disease Embryo Mammalian Molecular biology nervous system diseases Up-Regulation RNA splicing Ataxia Sequence Alignment Gene Deletion |
Zdroj: | ResearcherID Stephen H. Pasternak |
Popis: | 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. |
Databáze: | OpenAIRE |
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