Arachidonic acid 5-lipoxygenase (ALOX5) is the key
enzyme in the biosynthesis of pro-inflammatory
leukotrienes. We recently created knock-in mice (Alox5-KI) which express an
arachidonic acid 15-lipoxygenating Alox5 mutant instead of the 5-lipoxygenating wildtype
enzyme. These mice were
leukotriene deficient but exhibited an elevated
linoleic acid oxygenase activity. Here we characterized the polyenoic
fatty acid metabolism of these mice in more detail and tested the animals in three different experimental
inflammation models. In
experimental autoimmune encephalomyelitis (EAE), Alox5-KI mice displayed an earlier disease onset and a significantly higher cumulative incidence rate than wildtype controls but the clinical score kinetics were not significantly different. In
dextran sodium sulfate-induced
colitis (DSS) and in the chronic constriction nerve injury model (CCI), Alox5-KI mice performed like wildtype controls with similar genetic background. These results were somewhat surprising since in previous loss-of-function studies targeting
leukotriene biosynthesis (Alox5-/- mice, inhibitor studies), more severe inflammatory symptoms were observed in the EAE model but the degree of
inflammation in DSS
colitis was attenuated. Taken together, our data indicate that these mutant Alox5-KI mice respond differently in two models of experimental
inflammation than Alox5-/- animals tested previously in similar experimental setups.