Expression of the G72/G30 gene in transgenic mice induces behavioral changes
| Autor: | Mark D. Opal, Elliot S. Gershon, Stephanie C. Dulawa, Nancy S. Woehrle, Eiji Hattori, Ya-Ping Tang, Kay Grennan, Lijun Cheng, Chunyu Liu, Chunling Zhang, Akira Nakajima |
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| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
Gene isoform
Genetically modified mouse Male Candidate gene Reflex Startle hedonic response Transgene Mice Transgenic Biology Article G72/G30 Cellular and Molecular Neuroscience Food Preferences Mice Species Specificity Gene expression Chlorocebus aethiops Testis Animals Humans Protein Isoforms RNA Messenger Molecular Biology Gene Motivation Mental Disorders Alternative splicing Intracellular Signaling Peptides and Proteins Brain Molecular biology Gene expression profiling Psychiatry and Mental health Alternative Splicing transgenic mouse model stereotypic behavior psychiatric disorders COS Cells gene expression Female Stereotyped Behavior Carrier Proteins Transcriptome |
| Zdroj: | Molecular psychiatry |
| ISSN: | 1476-5578 1359-4184 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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