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Published on: April 13, 2017
Unchanged survival rates of 14-3-3gamma knockout mice after inoculation with pathological prion protein
Petra Steinacker1, Petra Schwarz, Kerstin Reim
1Neurologische Klinik und Poliklinik, Georg-August-Universität Göttingen, Robert-Koch-Strasse 40, 37075 Göttingen, Germany.
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.
Insights
14-3-3gamma protein is not essential for prion disease progression. This study found no differences in survival rates between knockout and wild-type mice infected with scrapie, suggesting 14-3-3gamma is not crucial for transmissible spongiform encephalopathies.
Area of Science:
- Neuroscience
- Molecular Biology
- Prion Diseases
Background:
- Sporadic Creutzfeldt-Jakob disease (CJD) diagnosis relies on clinical findings and 14-3-3 Western blot in cerebrospinal fluid.
- The pathophysiological role and origin of 14-3-3 proteins in CJD remain unclear.
- The distinct isoform spectrum in cerebrospinal fluid suggests a regulated process, not just general neuronal damage.
Purpose of the Study:
- To investigate the role of 14-3-3gamma in transmissible spongiform diseases.
- To determine if 14-3-3gamma deficiency impacts disease progression or survival in a mouse model of prion disease.
Main Methods:
- Generation of a 14-3-3gamma-deficient mutant mouse line using classical knockout strategy.
- Analysis of mouse anatomy, behavior, and brain protein expression (Western blot, proteomics).
- Intracerebral and intraperitoneal inoculation of mutant and wild-type mice with Rocky Mountain Laboratory strain of scrapie.
Main Results:
- 14-3-3gamma-deficient mice exhibited normal anatomy and behavior.
- No changes in expression of other 14-3-3 isoforms were observed in mutant mouse brains.
- Proteomic analysis revealed differential expression of several proteins, including growth hormone and alpha-SNAP.
- No significant difference in postinoculation survival rates between mutant and wild-type mice challenged with scrapie.
Conclusions:
- 14-3-3gamma is unlikely to play a causal role in the pathogenesis of CJD and related transmissible spongiform diseases.
- The study indicates that 14-3-3gamma is not essential for disease progression in this scrapie model.
- Further research may be needed to elucidate the precise role of other 14-3-3 isoforms in prion diseases.
