Deletion of protease-activated receptor 2 prolongs survival of scrapie-inoculated mice.
Proteinase-activated receptor 2 (PAR2) has recently been identified to be a possible modulator of neurodegeneration. To investigate whether PAR2 plays a role in prion infection, we inoculated PAR2-deficient (PAR2(-/-)) and wild-type (WT) mice intracerebrally with the Rocky Mountain Laboratory strain of scrapie. PAR2(-/-) mice demonstrated a delayed onset of clinical symptoms, including weight loss, and demonstrated moderate but highly significant prolongation of survival over WT controls. Concomitantly, no apparent differences in brain pathology, infectivity or features of brain prion protein between deceased WT and PAR2(-/-) mice were found. Our study suggests that PAR2 deletion modulates dynamics of the disease without gross perturbation of its pathogenesis.
Department of Pathology, Third Faculty of Medicine, Charles University in Prague, Ruska 87, Prague 10, 100 00, Czech Republic.|Department of Pathology and Molecular Medicine, Thomayer Teaching Hospital, Videnska 800, Prague 4, 140 59, Czech Republic.
Radoslav
R
Matej
Department No. 75, Institute of Physiology, Academy of Sciences of the Czech Republic, Videnska 1083, Prague 4, 142 20, Czech Republic.|Department of Pathology and Molecular Medicine, Thomayer Teaching Hospital, Videnska 800, Prague 4, 140 59, Czech Republic.
Tomas
T
Olejar
Institute of Immunology and Microbiology, First Faculty of Medicine, Charles University in Prague, Studnickova 7, Prague 2, 128 20, Czech Republic.
Olga
O
Janouskova
Institute of Immunology and Microbiology, First Faculty of Medicine, Charles University in Prague, Studnickova 7, Prague 2, 128 20, Czech Republic.
Karel
K
Holada
D000818:Animals; D005260:Female; D017353:Gene Deletion; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011328:Prions / Q000235:genetics / Q000378:metabolism; D044464:Receptor, PAR-2 / Q000172:deficiency / Q000235:genetics*; D012608:Scrapie / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism / Q000401:mortality*
D011328:Prions; D044464:Receptor, PAR-2