title: Behavioral and pharmacological phenotypes of brain-specific diacylglycerol kinase δ-knockout mice.
abstract: Diacylglycerol kinase (DGK) is a lipid-metabolizing enzyme that phosphorylates diacylglycerol to produce phosphatidic acid. Previously, we reported that the δ isozyme of DGK was abundantly expressed in the mouse brain. However, the functions of DGKδ in the brain are still unclear. Because conventional DGKδ-knockout (KO) mice die within 24h after birth, we have generated brain-specific conditional DGKδ-KO mice to circumvent the lethality. In the novel object recognition test, the number of contacts in the DGKδ-KO mice to novel and familiar objects was greatly increased compared to the control mice, indicating that the DGKδ-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 DGKδ-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 DGKδ-KO mice showed OCD-like behaviors. Moreover, the number of long axon/neurites increased in both DGKδ-KO primary cortical neurons and DGKδ-knockdown neuroblastoma Neuro-2a cells compared to control cells. Conversely, overexpression of DGKδ decreased the number of long axon/neurites of Neuro-2a cells. Taken together, these results strongly suggest that a deficiency of DGKδ induces OCD-like behavior through enhancing axon/neurite outgrowth.
authors.affiliation: Department of Chemistry, Graduate School of Science, Chiba University, 1-33 Yayoi-cho, Inage-ku, Chiba 263-8522, Japan.
authors.forename: Takako
authors.initials: T
authors.lastname: Usuki
authors.affiliation: Department of Chemistry, Graduate School of Science, Chiba University, 1-33 Yayoi-cho, Inage-ku, Chiba 263-8522, Japan.
authors.forename: Tamae
authors.initials: T
authors.lastname: Takato
authors.affiliation: Department of Chemistry, Graduate School of Science, Chiba University, 1-33 Yayoi-cho, Inage-ku, Chiba 263-8522, Japan.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Lu
authors.affiliation: Department of Chemistry, Graduate School of Science, Chiba University, 1-33 Yayoi-cho, Inage-ku, Chiba 263-8522, Japan.
authors.forename: Hiromichi
authors.initials: H
authors.lastname: Sakai
authors.affiliation: Animal Resource Development Unit and Genetic Engineering Team, Riken Center for Life Science Technologies, 2-2-3, Minatojima, Minami-machi, Chuo-ku, Kobe 650-0047, Japan.
authors.forename: Kana
authors.initials: K
authors.lastname: Bando
authors.affiliation: Animal Resource Development Unit and Genetic Engineering Team, Riken Center for Life Science Technologies, 2-2-3, Minatojima, Minami-machi, Chuo-ku, Kobe 650-0047, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kiyonari
authors.affiliation: Department of Chemistry, Graduate School of Science, Chiba University, 1-33 Yayoi-cho, Inage-ku, Chiba 263-8522, Japan. Electronic address: sakane@faculty.chiba-u.jp.
authors.forename: Fumio
authors.initials: F
authors.lastname: Sakane
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology*; D001921:Brain / Q000201:enzymology*; D045744:Cell Line, Tumor; D019852:Diacylglycerol Kinase / Q000235:genetics / Q000502:physiology*; D005260:Female; D005473:Fluoxetine / Q000008:administration & dosage; D007527:Isoenzymes / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016501:Neurites / Q000201:enzymology; D009771:Obsessive-Compulsive Disorder / Q000201:enzymology*; D010641:Phenotype; D021641:Recognition, Psychology / Q000502:physiology; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage
chemical_list: D019852:Diacylglycerol Kinase; D005473:Fluoxetine; D007527:Isoenzymes; D017367:Selective Serotonin Reuptake Inhibitors
keywords: Diacylglycerol kinase; Fluoxetine; Neurite; Obsessive-compulsive disorder; Phosphatidic acid