Purkinje-cell degeneration in prion protein-deficient mice is associated with a cerebellum-specific Doppel protein species signature |
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Authors: | Al Bersaoui Roméo Robert Isabelle Lutz Yves Blanc Frédéric Sommermeyer-Leroux Ghislaine Shibaguchi Hirotomo Aunis Dominique Fuchs Jean-Paul |
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Affiliation: | Unité 575 INSERM, Physiopathologie du Système Nerveux, Strasbourg, France. |
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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. |
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Keywords: | Dpl, Doppel protein PrPc, cellular prion protein Prnd, mouse Doppel protein gene Prnp, mouse prion protein gene Prn, mouse Prnp and Prnd locus PC, Purkinje cell mAb, monoclonal antibody pAb, polyclonal antibody PNGase F, peptide-N-glycosidase F LDS, lithium dodecyl sulfate MES, 2-(N-morpholino)ethanesulfonic acid |
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