Scrg1 is induced in TSE and brain injuries, and associated with autophagy.
We have previously identified Scrg1, a gene with increased cerebral mRNA levels in transmissible spongiform encephalopathies (TSE) such as scrapie, bovine spongiform encephalopathy and Creutzfeldt-Jakob disease. In this study, Scrg1-immunoreactive cells, essentially neurons, were shown to be widely distributed throughout the brain of scrapie-infected mice, while only rare and weakly immunoreactive cells could be detected in the brain of non-infected normal mice. Induction of the protein was confirmed by Western blot analysis. At the ultrastructural level, Scrg1 protein was associated with dictyosomes of the Golgi apparatus and autophagic vacuoles in the central neurons of the scrapie-infected mice. These results suggested a role for Scrg1 in the pathological changes observed in TSE. We have generated transgenic mice specifically expressing Scrg1 in neurons. No significant differences in the time course of the disease were detected between transgenic and non-transgenic mice infected with scrapie prions. However, tight association of Scrg1 with autophagic vacuoles was again observed in brain neurons of infected transgenic mice. High levels of the protein were also detected in degenerating Purkinje cells of Ngsk Prnp 0/0 mice overexpressing the Prnd gene coding for doppel, a neurotoxic paralogue of the prion protein. Furthermore, induction of Scrg1 protein was observed in the brain of mice injured by canine distemper virus or gold thioglucose treatment. Taken together, our results indicate that Scrg1 is associated with neurodegenerative processes in TSE, but is not directly linked to dysregulation of prion protein.
Dron
Michel
M
CNRS UPR-9045, Laboratoire d'Oncologie Virale, 7 rue Guy Môquet BP-8, 94801 Villejuif Cedex, France.
Bailly
Yannick
Y
Beringue
Vincent
V
Haeberlé
Anne-Marie
AM
Griffond
Bernadette
B
Risold
Pierre-Yves
PY
Tovey
Michael G
MG
Laude
Hubert
H
Dandoy-Dron
Françoise
F
D000818:Animals; D006051:Aurothioglucose / Q000494:pharmacology; D001343:Autophagy / Q000235:genetics*; D001921:Brain / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D004195:Disease Models, Animal; D004217:Distemper Virus, Canine / Q000235:genetics / Q000378:metabolism; D058851:GPI-Linked Proteins; D006056:Golgi Apparatus / Q000473:pathology / Q000648:ultrastructure; D007150:Immunohistochemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D046529:Microscopy, Electron, Transmission; D009410:Nerve Degeneration / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D018620:PrPSc Proteins / Q000235:genetics / Q000378:metabolism; D017096:Prion Diseases / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D011328:Prions / Q000235:genetics / Q000378:metabolism*; D014617:Vacuoles / Q000473:pathology / Q000648:ultrastructure
D058851:GPI-Linked Proteins; D009419:Nerve Tissue Proteins; D018620:PrPSc Proteins; D011328:Prions; C122036:Prnd protein, mouse; C111496:Scrg1 protein, mouse; D006051:Aurothioglucose