title: Ncf1 (p47phox) polymorphism determines oxidative burst and the severity of arthritis in rats and mice.
abstract: Identifying genes that regulate polygenic diseases influenced by the environment such as rheumatoid arthritis (RA), has so far proven to be difficult. By using an alternative approach, i.e., linkage analysis using relevant animal models we succeeded in finding the Ncf1 gene residing in the Pia4 quantitative trait locus to be responsible for the severity of pristane induced arthritis in rats. The influence of another mutation in the mouse Ncf1 gene showed the same association between decreased oxidative burst and enhanced arthritis. In this case the mutation affected a splice site giving a non-detectable oxidative burst response and enhanced collagen induced arthritis as well as myelin oligodendrocyte protein induced experimental autoimmune encephalomyelitis. These findings open up new possibilities for new treatments for autoimmune diseases, i.e., RA, targeting the NADPH oxidase pathway.
authors.affiliation: Section for Medical Inflammation Research, Lund University, Lund, Sweden.
authors.forename: Malin
authors.initials: M
authors.lastname: Hultqvist
authors.forename: Rikard
authors.initials: R
authors.lastname: Holmdahl
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000139:chemically induced / Q000235:genetics* / Q000378:metabolism*; D051379:Mice; D019255:NADPH Oxidases; D010750:Phosphoproteins / Q000172:deficiency / Q000235:genetics* / Q000502:physiology; D011110:Polymorphism, Genetic; D051381:Rats; D016897:Respiratory Burst / Q000235:genetics*; D012720:Severity of Illness Index
chemical_list: D010750:Phosphoproteins; D019255:NADPH Oxidases; C060505:neutrophil cytosolic factor 1