Glutamate receptor metabotropic 7 is cis-regulated in the mouse brain and modulates alcohol drinking
| Autor: | Mariko Saito, Melinda Oros, Vidudala V. T. S. Prasad, Beatrix M. Gyetvai, Reka Toth, Istvan Szakall, Csaba Vadasz, Krisztina M. Kovacs |
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| Rok vydání: | 2007 |
| Předmět: |
Male
Genetic Linkage QTL media_common.quotation_subject Molecular Sequence Data Mice Inbred Strains Alcohol drinking Physical dependence Biology Receptors Metabotropic Glutamate Polymorphism Single Nucleotide Mice Mice Congenic Dopamine Recombinant QTL introgression Genetics medicine Animals Elméleti orvostudományok RNA Messenger Promoter Regions Genetic Receptor Crosses Genetic Oligonucleotide Array Sequence Analysis media_common Polymorphism Genetic Base Sequence Gene Expression Profiling RQI Addiction Glutamate receptor Brain Chromosome Mapping Orvostudományok DNA Alcoholism Metabotropic receptor Gene Expression Regulation Gene identification Metabotropic glutamate receptor Models Animal medicine.symptom Psychiatric disorders Neuroscience QTG medicine.drug Ionotropic effect |
| Zdroj: | Genomics. 90:690-702 |
| ISSN: | 0888-7543 |
| DOI: | 10.1016/j.ygeno.2007.08.006 |
| Popis: | Alcoholism is a heritable disease that afflicts about 8% of the adult population. Its development and symptoms, such as craving, loss of control, physical dependence, and tolerance, have been linked to changes in mesolimbic, mesocortical neurotransmitter systems utilizing biogenic amines, GABA, and glutamate. Identification of genes predisposing to alcoholism, or to alcohol-related behaviors in animal models, has been elusive because of variable interactions of multiple genes with relatively small individual effect size and sensitivity of the predisposing genotype to lifestyle and environmental factors. Here, using near-isogenic advanced animal models with reduced genetic background interactions, we integrate gene mapping and gene mRNA expression data in segregating and congenic mice and identify glutamate receptor metabotropic 7 (Grm7) as a cis-regulated gene for alcohol consumption. Traditionally, the mesoaccumbal dopamine reward hypothesis of addiction and the role of the ionotropic glutamate receptors have been emphasized. Our results lend support to an emerging direction of research on the role of metabotropic glutamate receptors in alcoholism and drug addiction. These data suggest for the first time that Grm7 is a risk factor for alcohol drinking and a new target in addiction therapy. |
| Databáze: | OpenAIRE |
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