Phenomic, convergent functional genomic, and biomarker studies in a stress-reactive genetic animal model of bipolar disorder and co-morbid alcoholism
| Autor: | Howard J. Edenberg, John I. Nurnberger, S D Patel, Corey A. Ogden, Stephen V. Faraone, J. Tan, Stephen J. Glatt, Yokesh Balaraman, M.J. McFarland, Alexander B. Niculescu, Ronald Kuczenski, Martin P. Paulus, Mark A. Geyer, Zachary A. Rodd, Helen Le-Niculescu, Ming T. Tsuang |
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| Rok vydání: | 2008 |
| Předmět: |
medicine.medical_specialty
Candidate gene Bipolar Disorder Microarray medicine.drug_class Genetic Linkage Mice Transgenic Comorbidity Biology Cellular and Molecular Neuroscience Mice Stress Physiological Internal medicine medicine Animals Humans Chronic stress Bipolar disorder Genetics (clinical) Genetics Genome Models Genetic Gene Expression Profiling Mood stabilizer medicine.disease Null allele DNA-Binding Proteins Psychiatry and Mental health Alcoholism Disease Models Animal Endocrinology Phenotype Knockout mouse Sleep Deprivation Functional genomics Biomarkers Transcription Factors |
| Zdroj: | American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics. (2) |
| ISSN: | 1552-485X |
| Popis: | We had previously identified the clock gene D-box binding protein (Dbp) as a potential candidate gene for bipolar disorder and for alcoholism, using a Convergent Functional Genomics (CFG) approach. Here we report that mice with a homozygous deletion of DBP have lower locomotor activity, blunted responses to stimulants, and gain less weight over time. In response to a chronic stress paradigm, these mice exhibit a diametric switch in these phenotypes. DBP knockout mice are also activated by sleep deprivation, similar to bipolar patients, and that activation is prevented by treatment with the mood stabilizer drug valproate. Moreover, these mice show increased alcohol intake following exposure to stress. Microarray studies of brain and blood reveal a pattern of gene expression changes that may explain the observed phenotypes. CFG analysis of the gene expression changes identified a series of novel candidate genes and blood biomarkers for bipolar disorder, alcoholism, and stress reactivity. |
| Databáze: | OpenAIRE |
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