Behavioral and pharmacological phenotypes of brain-specific diacylglycerol kinase δ-knockout mice

Diacylglycerol kinase (DGK) is a lipid-metabolizing enzyme that phosphorylates diacylglycerol to produce phosphatidic acid. Previously, we reported that the delta isozyme of DGK was abundantly expressed in the mouse brain. However, the functions of DGKS in the brain are still unclear. Because conventional DGK delta-knockout (KO) mice die within 24 h after birth, we have generated brain-specific conditional DGK delta-KO mice to circumvent the lethality. In the novel object recognition test, the number of contacts in the DGK delta-KO mice to novel and familiar objects was greatly increased compared to the control mice, indicating that the DGK delta-KO mice showed irrational contacts with objects such as compulsive checking. In the marble burying test, which is used for analyzing obsessive-compulsive disorder (OCD)-like phenotypes, the DGK delta-KO mice buried more marbles than the control mice. Additionally, these phenotypes were significantly alleviated by the administration of an OCD remedy, fluoxetine. These results indicate that the DGK delta-KO mice showed OCD-like behaviors. Moreover, the number of long axon/neurites increased in both DGK delta-KO primary cortical neurons and DGK delta-knockdown neuroblastoma Neuro-2a cells compared to control cells. Conversely, overexpression of DGK delta decreased the number of long axon/ neurites of Neuro-2a cells. Taken together, these results strongly suggest that a deficiency of DGK delta induces OCD-like behavior through enhancing axonineurite outgrowth. (C) 2016 Elsevier B.V. All rights reserved.