NR AOZJ
AU Steinacker,P.; Schwarz,P.; Aguzzi,A.; Aitken,A.; Brose,N.; Otto,M.
TI Unchanged survival curves of 14-3-3 gamma knock-out mice after inoculation with pathological prion protein
QU International Conference - Prion diseases: from basic research to intervention concepts - TSE-Forum, 08.10.-10.10.2003, Gasteig, München - Poster session - PG-25
PT Konferenz-Poster
AB
Background:
The clinical diagnosis of sporadic CJD is based on typical clinical findings and is supported by a positive 14-3-3 Western blot (WB) of cerebrospinal fluid (CSF). However, it is unclear whether the positive 14-3-3 WB indicates a general neuronal damage or if 14-3-3 proteins are of pathophysiological relevance in CJD. The fact that the 14-3-3 isoform spectrum in CSF does not correspond to the spectrum found in brain points to a regulated process. The most abundant isoform in brain is the 14-3-3 gamma isoform. This isoform is also most abundant in CSF.
Methods and Results:
To investigate a possible role of 14-3-3 proteins in transmissible spongiform diseases, we generated a 14-3-3 gamma deletion mutant mouse line using a classical knock-out strategy. Anatomy and cage behaviour of deletion mutant mice were normal. WB analyses of brain homogenates revealed no changes in the protein expression of other 14-3-3 isoforms (beta, eta, epsilon, zeta).
Mutant mice as well as wild type control mice were then inoculated either intracerebrally or intraperitoneally with the RML strain. No differences in the post-inoculation survival curves were detected between deletion mutant and wild type mice.
Conclusion:
These results demonstrate that at least loss of the most abundant 14-3-3 isoform has no effect on survival after inoculation with the RML strain.
AD P. Steinacker, M. Otto, Department of Neurology, University of Göttingen, Germany; P. Schwarz, A. Aguzzi, Department of Neuropathology, University of Zürich, Switzerland; A. Aitken, Department of Biomedical Sciences, Edinburgh, Scotland; N. Brose, MPI for Experimental Medicine, Göttingen, Germany
SP englisch
PO Deutschland