title: Purkinje-cell degeneration in prion protein-deficient mice is associated with a cerebellum-specific Doppel protein species signature.
abstract: PrP(c) (cellular prion protein) and Doppel are antagonizing proteins, respectively neuroprotective and neurotoxic. Evidence for Doppel neurotoxicity came from PrP(c)-deficient (Prnp(0/0)) mouse lines developing late onset Purkinje-cell degeneration caused by Doppel overexpression in brain. To address the molecular underpinnings of this cell-type specificity, we generated Doppel N-terminal-specific antibodies and started to examine the spatio-temporal expression of Doppel protein species in Ngsk Prnp(0/0) brain. Although Doppel overexpression is ubiquitous, Western analyses of normal and deglycosylated protein extracts revealed cerebellar patterns distinct from the rest of the brain, supporting the idea that neurotoxicity might be linked to a particular Doppel species pattern. Furthermore, our newly raised antibodies allowed the first Doppel immunohistochemical analyses in brain, showing a distribution in Prnp(0/0) cerebellum similar to PrP(c) in wild type.
authors.affiliation: Unité 575 INSERM, Physiopathologie du Système Nerveux, Strasbourg, France.
authors.forename: Roméo
authors.initials: R
authors.lastname: Al Bersaoui
authors.forename: Isabelle
authors.initials: I
authors.lastname: Robert
authors.forename: Yves
authors.initials: Y
authors.lastname: Lutz
authors.forename: Frédéric
authors.initials: F
authors.lastname: Blanc
authors.forename: Ghislaine
authors.initials: G
authors.lastname: Sommermeyer-Leroux
authors.forename: Hirotomo
authors.initials: H
authors.lastname: Shibaguchi
authors.forename: Dominique
authors.initials: D
authors.lastname: Aunis
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Fuchs
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002531:Cerebellum / Q000737:chemistry*; D058851:GPI-Linked Proteins; D007150:Immunohistochemistry; D051379:Mice; D018345:Mice, Knockout; D009410:Nerve Degeneration / Q000473:pathology*; D016133:Polymerase Chain Reaction; D011328:Prions / Q000235:genetics / Q000378:metabolism*; D011689:Purkinje Cells / Q000473:pathology*; D011994:Recombinant Proteins / Q000378:metabolism
chemical_list: D058851:GPI-Linked Proteins; D011328:Prions; C122036:Prnd protein, mouse; D011994:Recombinant Proteins