| A genetic screen for behavioral mutations that perturb dopaminergic homeostasis in mice. | |
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MedLine Citation:
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PMID: 16436185 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Disruption of dopaminergic (DA) systems is thought to play a central role in the addictive process and in the pathophysiology of schizophrenia. Although inheritance plays an important role in the predisposition to these disorders, the genetic basis of this is not well understood. To provide additional insight, we have performed a modifier screen in mice designed to identify mutations that perturb DA homeostasis. With a genetic background sensitized by a mutation in the dopamine transporter (DAT), we used random chemical mutagenesis and screened for mutant mice with locomotor abnormalities. Four mutant lines were identified with quantitatively elevated levels of locomotor activity. Mapping of mutations in these lines identified two loci that alter activity only when dopamine levels are elevated by a DAT mutation and thus would only have been uncovered by this type of approach. One of these quantitative trait loci behaves as an enhancer of DA neurotransmission, whereas the other may act as a suppressor. In addition, we also identified three loci which are not dependent on the sensitized background but which also contribute to the overall locomotor phenotype. |
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Authors:
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D J Speca; N Rabbee; D Chihara; T P Speed; A S Peterson |
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Publication Detail:
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Type: Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S. |
Journal Detail:
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Title: Genes, brain, and behavior Volume: 5 ISSN: 1601-1848 ISO Abbreviation: Genes Brain Behav. Publication Date: 2006 Feb |
Date Detail:
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Created Date: 2006-01-26 Completed Date: 2006-05-03 Revised Date: 2009-11-19 |
Medline Journal Info:
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Nlm Unique ID: 101129617 Medline TA: Genes Brain Behav Country: England |
Other Details:
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Languages: eng Pagination: 19-28 Citation Subset: IM |
Affiliation:
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Department of Neurology and the Ernest Gallo Clinic and Research Center, University of California at San Francisco, Emeryville, CA 94608, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Chromosome Mapping Dopamine / metabolism* Dopamine Plasma Membrane Transport Proteins / genetics, metabolism* Ethylnitrosourea Exploratory Behavior / physiology* Female Genetic Testing* Heterozygote Detection Homeostasis / genetics* Homozygote Male Mice Mice, Inbred DBA Mice, Knockout Motor Activity / genetics* Mutagenesis / genetics* Mutagens Phenotype Quantitative Trait Loci / genetics Random Allocation |
| Chemical | |
Reg. No./Substance:
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0/Dopamine Plasma Membrane Transport Proteins; 0/Mutagens; 759-73-9/Ethylnitrosourea |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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