5-lipoxygenase (5LOX)-deficient mice express reduced anxiety-like behavior

5-Lipoxygenase (5LOX) is an enzyme critical for leukotriene synthesis from arachidonic acid. In addition to its role in peripheral inflammation, this enzyme is also expressed in the brain but its functional role in the central nervous system is poorly understood. An upregulated expression of brain 5LOX, for example during aging and in multiple sclerosis, has been associated with increased vulnerability to neurodegeneration. Moreover, the 5LOX pathway has been associated with the neurotoxicity of the prion peptide. 5LOX-deficient mice [5LOX(-); B6129S(Alox5tm1Fun)] and their controls (B6129SF2/J) have not been behaviorally characterized.

The following behavioral tests were used for behavioral characterization of 5LOX(-) mice: elevated plus-maze, marble burying, locomotor activity, rota-road, and the spontaneous alternations in T-maze.

We found that in an elevated plus-maze, 5LOX(-) mice spent a shorter time in the "safe" closed arms, a longer time in the "anxiogenic" open arms, and entered the open arms more frequently. They also covered fewer marbles in the marble-burying anxiety test. No difference was observed between 5LOX(-) and 5LOX(+) mice in other tests.

These results indicate that 5LOX(-) mice are less prone to anxiety and point to a possible role for 5LOX in affective behaviors. We propose that creating congenic 5LOX(-) mice by backcrossing into inbred strains would provide additional tools to further elucidate this putative role.