Spongiform encephalopathies: insights from transgenic models.
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Biomedical subjects
Publications and source records attributed to C Röckl.
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Spongiform encephalopathies are a group of infectious neurodegenerative diseases. The infectious agent that causes transmissible spongiform encephalopathies was termed prion by Stanley Prusiner. The prion hypothesis states that the partially protease-resistant and detergent-insoluble prion protein (PrPsc) is identical with the infectious agent, and lacks any detectable nucleic acids. Since the latter discovery, transgenic mice have contributed many important insights into the field of prion biology. The prion protein (PrPc) is encoded by the Prnp gene, and disruption of Prnp leads to resistance to infection by prions. Introduction of mutant PrPc genes into PrPc-deficient mice was used to investigate structure-activity relationships of the PrPc gene with regard to scrapie susceptibility. Ectopic expression of PrPc in PrPc knockout mice proved a useful tool for the identification of host cells competent for prion replication. Finally, the availability of PrPc knockout and transgenic mice overexpressing PrPc allowed selective reconstitution experiments aimed at expressing PrPc in neurografts or in specific populations of hemato- and lymphopoietic cells. The latter studies helped in elucidating some of the mechanisms of prion spread and disease pathogenesis.
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Classification (119 patients) of age, sex and side distributions and the frequency of additional fibromatoses or other diseases in palmar fibromatosis (Morbus Dupuytren) showed extensive agreement with other investigations. Contractures were also found in mutiple foci with high cell density and without intensive collagen fiber formation corresponding to the proliferative or involution phase. Cells with contractile elements ("myofibroblasts") could also be demonstrated with both electron and immunofluorescence microscopes. These elements may be of importance for the formation of the contracture in palmar fibromatosis and may disappear again as the collagen becomes more mature.