Kynurenine Aminotransferase II Knockout Mice Mimic Depression with Psychomotor Retardation

Major depressive disorder (MDD) exhibits negative emotional symptoms with various degrees of psychomotor manifestation. The disturbance of the tryptophan-kynurenine (KYN) metabolic system has been implicated in MDD. Kynurenine/α-aminoadipate aminotransferase (KAT II) is a mitochondrial enzyme that catalyzes the reaction of KYN to kynurenic acid. Little is known about the impact of the gene aadat knockout (KAT II KO^-/-) on behaviors. We studied negative emotional and motor domains at 4 and 12 weeks of male KAT II KO^-/- mice and the wild-type counterpart C57BL/6N.

Depression-like, anxiety-like, and motor behaviors were assessed by modified forced swim test (FST), elevated plus-maze (EPM) test, light-dark box (LDB) test, and open field (OF) test.

FST showed significantly more depression-like behaviors at 4 and 12 weeks in KAT II KO^-/- mice than the wild-type and the older mice were more prominent in both strains. Both strains spent significantly more time in the light at week 12 than week 4 in LDB test. The OF test showed significantly shorter ambulation time at week 12 in KAT II KO^-/- mice than the wild-type and significantly longer time spent in the center zone at week 12 than week 4 in both strains.

We show here that KAT II KO^-/- mice exhibit more depression-like behaviors in an age-dependent manner, accompanied with decreasing anxiety and motor activity. Thus, the aadat gene knock-out influences behavioral domains in such a manner that the strain potentially serves as an animal model of a subtype, depression with psychomotor retardation.