First Author | Usuki T | Year | 2016 |
Journal | Brain Res | Volume | 1648 |
Issue | Pt A | Pages | 193-201 |
PubMed ID | 27423518 | Mgi Jnum | J:235943 |
Mgi Id | MGI:5804038 | Doi | 10.1016/j.brainres.2016.07.017 |
Citation | Usuki T, et al. (2016) Behavioral and pharmacological phenotypes of brain-specific diacylglycerol kinase delta-knockout mice. Brain Res 1648(Pt A):193-201 |
abstractText | 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 DGKdelta in the brain are still unclear. Because conventional DGKdelta-knockout (KO) mice die within 24h after birth, we have generated brain-specific conditional DGKdelta-KO mice to circumvent the lethality. In the novel object recognition test, the number of contacts in the DGKdelta-KO mice to novel and familiar objects was greatly increased compared to the control mice, indicating that the DGKdelta-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 DGKdelta-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 DGKdelta-KO mice showed OCD-like behaviors. Moreover, the number of long axon/neurites increased in both DGKdelta-KO primary cortical neurons and DGKdelta-knockdown neuroblastoma Neuro-2a cells compared to control cells. Conversely, overexpression of DGKdelta decreased the number of long axon/neurites of Neuro-2a cells. Taken together, these results strongly suggest that a deficiency of DGKdelta induces OCD-like behavior through enhancing axon/neurite outgrowth. |