title: Expression of the G72/G30 gene in transgenic mice induces behavioral changes.
abstract: The G72/G30 gene complex is a candidate gene for schizophrenia and bipolar disorder. However, G72 and G30 mRNAs are expressed at very low levels in human brain, with only rare splicing forms observed. We report here G72/G30 expression profiles and behavioral changes in a G72/G30 transgenic mouse model. A human BAC clone containing the G72/G30 genomic region was used to establish the transgenic mouse model, on which gene expression studies, western blot and behavioral tests were performed. Relative to their minimal expression in humans, G72 and G30 mRNAs were highly expressed in the transgenic mice, and had a more complex splicing pattern. The highest G72 transcript levels were found in testis, followed by cerebral cortex, with very low or undetectable levels in other tissues. No LG72 (the long putative isoform of G72) protein was detected in the transgenic mice. Whole-genome expression profiling identified 361 genes differentially expressed in transgenic mice compared with wild-type, including genes previously implicated in neurological and psychological disorders. Relative to wild-type mice, the transgenic mice exhibited fewer stereotypic movements in the open field test, higher baseline startle responses in the course of the prepulse inhibition test, and lower hedonic responses in the sucrose preference test. The transcriptome profile changes and multiple mouse behavioral effects suggest that the G72 gene may play a role in modulating behaviors relevant to psychiatric disorders.
authors: Department of Psychiatry, Institute of Human Genetics, The University of Illinois at Chicago, Chicago, IL, USA.
authors: L
authors: L
authors: Cheng
authors: Laboratory for Molecular Psychiatry, RIKEN Brain Science Institute, Saitama 351-0198, and Sangenjaya Station Mental Health Clinic, Tokyo, Japan.
authors: E
authors: E
authors: Hattori
authors: Department of Neuropsychopharmacology and Hospital Pharmacy, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors: A
authors: A
authors: Nakajima
authors: Department of Psychiatry and Behavioral Neuroscience, University of Chicago, Chicago, IL, USA.
authors: N S
authors: NS
authors: Woehrle
authors: Department of Psychiatry and Behavioral Neuroscience, University of Chicago, Chicago, IL, USA.
authors: M D
authors: MD
authors: Opal
authors: Department of Psychiatry, Institute of Human Genetics, The University of Illinois at Chicago, Chicago, IL, USA.
authors: C
authors: C
authors: Zhang
authors: Department of Psychiatry and Behavioral Neuroscience, University of Chicago, Chicago, IL, USA.
authors: K
authors: K
authors: Grennan
authors: Department of Psychiatry and Behavioral Neuroscience, University of Chicago, Chicago, IL, USA.
authors: S C
authors: SC
authors: Dulawa
authors: Department of Cell Biology and Anatomy, Louisiana State University Health Sciences Center, New Orleans, LA, USA.
authors: Y-P
authors: YP
authors: Tang
authors: Department of Psychiatry and Behavioral Neuroscience, University of Chicago, Chicago, IL, USA.
authors: E S
authors: ES
authors: Gershon
authors: Department of Psychiatry, Institute of Human Genetics, The University of Illinois at Chicago, Chicago, IL, USA.
authors: C
authors: C
authors: Liu
mesh_terms: D017398:Alternative Splicing; D000818:Animals; D001921:Brain / Q000378:metabolism; D019556:COS Cells; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism*; D002522:Chlorocebus aethiops; D005260:Female; D005518:Food Preferences / Q000502:physiology; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D001523:Mental Disorders / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D009042:Motivation / Q000502:physiology*; D020033:Protein Isoforms / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013216:Reflex, Startle / Q000502:physiology*; D013045:Species Specificity; D013239:Stereotyped Behavior / Q000502:physiology*; D013737:Testis / Q000378:metabolism; D059467:Transcriptome
chemical_list: D002352:Carrier Proteins; C475071:DAOA protein, human; D047908:Intracellular Signaling Peptides and Proteins; D020033:Protein Isoforms; D012333:RNA, Messenger