Bax-ablation attenuates experimental autoimmune encephalomyelitis in mice.
Multiple sclerosis (MS) is an inflammatory disease of the central nervous system characterized by demyelination and axonal damage. Although the exact pathophysiology is unknown, apoptosis plays a crucial role. Here, we studied the role of the pro-apoptotic gene Bax in myelin oligodendrocyte glycoprotein (MOG)-induced experimental autoimmune encephalomyelitis (EAE), the animal model for MS. We demonstrate that the clinical signs were markedly reduced in the EAE Bax-deficient mice as compared to wild type (2.3 +/- 0.5 vs. 1.02 +/- 0.32, respectively, P < 0.05). Bax-deficient mice demonstrated less inflammatory infiltration and axonal damage, although they showed similar T-cell immune potency. In conclusion, ablation of the bax gene attenuates the severity of MOG-induced EAE and emphasizes the importance of apoptosis in the pathogenesis of EAE and MS.
Lev
Nirit
N
Felsenstein Medical Research Center, Beilinson Campus, Tel Aviv University, Sackler School of Medicine, Petah-Tikva, Israel.
Barhum
Yael
Y
Melamed
Eldad
E
Offen
Daniel
D
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001369:Axons / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000139:chemically induced / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D005786:Gene Expression Regulation / Q000187:drug effects; D051379:Mice; D009103:Multiple Sclerosis / Q000139:chemically induced / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein; D011518:Proto-Oncogene Proteins / Q000172:deficiency* / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2; D012720:Severity of Illness Index; D013116:Spinal Cord / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D051028:bcl-2-Associated X Protein
C494827:Bax protein, mouse; C571327:Mog protein, mouse; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein