Comprehensive behavioral analysis of tryptophan 2,3‐dioxygenase (Tdo2) knockout mice

Abstract

Abstract Aims Tryptophan 2,3‐dioxygenase (TDO2) is an initial rate‐limiting enzyme of the kynurenine (Kyn) pathway in tryptophan (Trp) metabolism. The Trp‐degrading enzymes, TDO2 and indoleamine 2,3‐dioxygenase, are activated by stress and/or inflammation. Dysregulation of Trp metabolism, which causes shifts in the balance between Kyn and serotonin (5‐HT) pathways, is associated with psychiatric and neurological disorders. In genetic studies, single‐nucleotide polymorphisms in the TDO2 gene were shown to be involved in psychiatric disorders, such as schizophrenia and depression. It has been reported that targeted deletion of the Tdo2 gene in mice resulted in reduced anxiety‐like behavior, enhanced exploratory activity and cognitive performance, and increased levels of Trp and 5‐HT in the hippocampus and midbrain. However, the effect of Tdo2 gene deletion on behavioral phenotypes has not yet been investigated extensively. Materials & Methods We conducted tests to further examine the behavioral effects of knockout (KO) of Tdo2 in mice. Results Deletion of Tdo2 resulted in seemingly lower anxiety‐like behavior, higher locomotor activity, and abnormal gait pattern in mice, though none of them reached study‐wide statistical significance. Tdo2 deficiency had no significant effects on other behaviors, such as prepulse inhibition, and depression‐like and social behaviors. Discussion and Conclusion He lack of clear phenotypes in Tdo2KO mice in this study might be due to the absence of stress and inflammatory conditions, which could induce expression of Tdo2 mRNA. Further studies are necessary to elucidate the roles of Tdo2 in behavioral phenotypes related to psychiatric disorders.

Keywords

• comprehensive behavioral test battery
• knockout mice
• kynurenine pathway
• tryptophan 2,3‐dioxygenase
• tryptophan metabolism