Physiological metabolic differences between Ncf1 mutant and wild type mice
(English)Manuscript (preprint) (Other academic)
The Ncf1 gene is a major determinant of disease severity in experimental animal models of Rheumatoid Arthritis. The Ncf1 codes a protein that is important for regulating the activity of the NADPH oxidase (NOX2) complex. This complex produces reactive oxygen species (ROS) important both for killing off pathogens but also for regulating the immune response.Using metabolic profiling techniques we have found that mutation of the Ncf1 gene leads to alteration of the metabolic profile even without induction of inflammation, thus demonstrating a physiological role for the gene. Transgenic expression of Ncf1 in macrophages restored the metabolic profile so it was very similar to that seen in wild type animals. This indicates that macrophages have an immune regulatory role even outside inflammation.The metabolic differences between genotypes were subtle so the experiments were repeated to ensure validity of the results. The most stable metabolic effect across studies was an increase in free fatty acids in animals with functional NOX2 oxidation. This is likely due to production of immune regulatory compounds in the pathways initiated by phospholipase A2.
Research subject biological chemistry
IdentifiersURN: urn:nbn:se:umu:diva-59476OAI: oai:DiVA.org:umu-59476DiVA: diva2:552457