title: Involvement of the primate specific gene G72 in schizophrenia: From genetic studies to pathomechanisms.
abstract: Schizophrenia is a human mental disorder that affects an individual's thoughts, perception, affect and behavior, which is caused by a complex interaction of genetic and environmental factors. Genetic studies have implicated the evolutionary novel, anthropoid primate-specific gene locus G72/G30 in the etiology of schizophrenia and other psychiatric disorders. This gene encodes the protein LG72, which has been discussed as a modulator of the peroxisomal enzyme d-amino-acid-oxidase (DAO), or, alternatively as a mitochondrial protein. Recently, G72 transgenic (G72Tg) mice were generated that express the protein throughout the brain. These mice show several behavioral deficits that are related to schizophrenia. Further, G72Tg mice have a reduced activity of mitochondrial complex I, with a concomitantly increased production of reactive oxygen species, as well as deficits in short-term plasticity. Results from these studies demonstrate that expression of the human G72/G30 gene locus in mice produces behavioral phenotypes that are relevant to schizophrenia. They implicate LG72-induced mitochondrial and synaptic defects as a possible pathomechanism of this disease.
authors.affiliation: Institute of Molecular Psychiatry, University of Bonn, Germany. Electronic address: edrews@uni-bonn.de.
authors.forename: Eva
authors.initials: E
authors.lastname: Drews
authors.forename: David-Marian
authors.initials: DM
authors.lastname: Otte
authors.forename: Andreas
authors.initials: A
authors.lastname: Zimmer
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D001921:Brain / Q000378:metabolism / Q000502:physiology; D002352:Carrier Proteins / Q000235:genetics* / Q000502:physiology*; D042967:Electron Transport Complex I / Q000172:deficiency / Q000235:genetics; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D008822:Mice, Transgenic; D028361:Mitochondrial Diseases / Q000235:genetics; D009473:Neuronal Plasticity / Q000235:genetics; D012559:Schizophrenia / Q000235:genetics* / Q000503:physiopathology*
chemical_list: D002352:Carrier Proteins; C475071:DAOA protein, human; D047908:Intracellular Signaling Peptides and Proteins; D042967:Electron Transport Complex I
keywords: G72 transgenic mice; Mitochondrial dysfunctions; Oxidative stress; Psychiatric disorders