NR AORO
AU Dandoy-Dron,F.; Griffond,B.; Mishal,Z.; Tovey,M.G.; Dron,M.
TI Role of Scrapie Responsive Gene One in TSE
QU International Conference - Prion diseases: from basic research to intervention concepts - TSE-Forum, 08.10.-10.10.2003, Gasteig, München - Poster session - PG-11
PT Konferenz-Poster
AB Scrapie Responsive Gene One (SCRG1) is a novel protein of the CNS discovered through identification of genes up-regulated in transmissible spongiform encephalopathies (TSE). Most of the molecules overexpressed in TSE are believed to be produced by glial cells and to reflect the astroglial cell activation associated with TSE. It has been proposed that these glial products may contribute to the development of pathological lesions in TSE. However, certain authors including ourselves, have established that transcripts of neuronal origin such as SCRG1 mRNA can be also up-regulated in TSE. The increase in SCRG1 mRNA in scrapie-infected mice occurs before the onset of the clinical signs of disease, suggesting a possible role for SCRG1 in the host response to TSE. In this study, we have generated antibodies against SCRG1 and characterized the 10kDa protein. The cerebellar Purkinje cells are identified as the principal site of SCRG1 expression in rodent brain. Two principal lines of evidence show that SCRG1 is targeted to dense-core vesicles in transfected neuronal cells. (i) SCRG1 is detected by immunofluorescence as very punctate signals especially in the Golgi apparatus and in neurites, suggesting a vesicular localization for the protein. Moreover SCRG1 exhibits a high degree of co-localization with Secretogranin II, a marker for dense-core vesicles and a very limited co-localization with markers for small synaptic vesicles (ii) SCRG1 immunoreactivity is associated to large dense-core vesicles, as indicated by electron microscopy. These findings and results showing the presence of SCRG1 in the culture medium of neuronal cells stably expressing the protein, strongly suggest that SCRG1 is a secretory protein. To further investigate the role of SCRG1 in TSE, we have produced transgenic mice overexpressing the protein in brain tissue and the animals will be inoculated with a strain of scrapie to test their prion susceptibility.
AD F. Dandoy-Dron, M.G. Tovey, M. Dron, Laboratoire d'Oncologie Virale-CNRS/UPR9045 (Institut A. Lwoff, France); B. Griffond, Laboratoire d'Histologie, Embryologie, Cytogénétique. (Faculté de Médecine et Pharmacie, Besançon, France); Z. Mishal, CNRS UPS 937 (Institut A. Lwoff, Villejuif, France)
SP englisch
PO Deutschland