title: Unchanged survival rates of 14-3-3gamma knockout mice after inoculation with pathological prion protein.
abstract: The diagnosis of sporadic Creutzfeldt-Jakob disease (CJD) is based on typical clinical findings and is supported by a positive 14-3-3 Western blot of cerebrospinal fluid. However, it is not clear whether 14-3-3 indicates general neuronal damage or is of pathophysiological relevance in CJD. The fact that the 14-3-3 isoform spectrum in cerebrospinal fluid does not correspond to that found in the brain points to a regulated process. To investigate a possible role of 14-3-3 proteins in transmissible spongiform diseases, we generated a 14-3-3gamma-deficient mutant mouse line by using a classical knockout strategy. The anatomy and cage behavior of the mutant mice were normal. Western blot analyses of brain homogenates revealed no changes in the protein expression of other 14-3-3 isoforms (epsilon, beta, zeta, and eta). Proteomic analyses of mouse brains by two-dimensional differential gel electrophoresis showed that several proteins, including growth hormone, 1-Cys peroxiredoxin, CCT-zeta, glucose-6-phosphate isomerase, GRP170 precursor, and alpha-SNAP, were differentially expressed. Mutant and wild-type mice were inoculated either intracerebrally or intraperitoneally with the Rocky Mountain Laboratory strain of scrapie, but no differences were detected in the postinoculation survival rates. These results indicate that 14-3-3gamma is unlikely to play a causal role in CJD and related diseases.
authors.affiliation: Neurologische Klinik und Poliklinik, Georg-August-Universität Göttingen, Robert-Koch-Strasse 40, 37075 Göttingen, Germany.
authors.forename: Petra
authors.initials: P
authors.lastname: Steinacker
authors.forename: Petra
authors.initials: P
authors.lastname: Schwarz
authors.forename: Kerstin
authors.initials: K
authors.lastname: Reim
authors.forename: Peter
authors.initials: P
authors.lastname: Brechlin
authors.forename: Olaf
authors.initials: O
authors.lastname: Jahn
authors.forename: Hartmut
authors.initials: H
authors.lastname: Kratzin
authors.forename: Alastair
authors.initials: A
authors.lastname: Aitken
authors.forename: Jens
authors.initials: J
authors.lastname: Wiltfang
authors.forename: Adriano
authors.initials: A
authors.lastname: Aguzzi
authors.forename: Erik
authors.initials: E
authors.lastname: Bahn
authors.forename: Helen C
authors.initials: HC
authors.lastname: Baxter
authors.forename: Nils
authors.initials: N
authors.lastname: Brose
authors.forename: Markus
authors.initials: M
authors.lastname: Otto
mesh_terms: D048948:14-3-3 Proteins / Q000134:cerebrospinal fluid / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D007562:Creutzfeldt-Jakob Syndrome / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D015180:Electrophoresis, Gel, Two-Dimensional; D051379:Mice; D018345:Mice, Knockout; D011328:Prions / Q000378:metabolism*; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D020543:Proteome / Q000378:metabolism*; D012608:Scrapie / Q000378:metabolism / Q000401:mortality; D015996:Survival Rate
chemical_list: D048948:14-3-3 Proteins; D011328:Prions; D020033:Protein Isoforms; D020543:Proteome