Tryptophan Hydroxylase-2 Controls Brain Serotonin Synthesis
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- 9 July 2004
- journal article
- Published by American Association for the Advancement of Science (AAAS) in Science
- Vol. 305 (5681) , 217
- https://doi.org/10.1126/science.1097540
Abstract
Dysregulation of brain serotonin contributes to many psychiatric disorders. Tryptophan hydroxylase-2 (Tph2), rather than Tph1, is preferentially expressed in the brain. We report a functional (C1473G) single-nucleotide polymorphism in mouse Tph2 that results in the substitution of Pro447 with Arg447 and leads to decreased serotonin levels in PC12 cells. Moreover, in BALB/cJ and DBA/2 mice that are homozygous for the 1473G allele, brain serotonin tissue content and synthesis are reduced in comparison to C57Bl/6 and 129X1/SvJ mice that are homozygous for the 1473C allele. Our data provide direct evidence for a fundamental role of Tph2 in brain serotonin synthesis.Keywords
This publication has 8 references indexed in Scilit:
- Experimental gene interaction studies with SERT mutant mice as models for human polygenic and epistatic traits and disordersGenes, Brain and Behavior, 2003
- Synthesis of Serotonin by a Second Tryptophan Hydroxylase IsoformScience, 2003
- An efficient procedure for genotyping single nucleotide polymorphismsNucleic Acids Research, 2001
- Sensitivity to the effects of pharmacologically selective antidepressants in different strains of micePsychopharmacology, 2001
- Dissecting the role of the serotonin system in neuropsychiatric disorders using knockout micePsychopharmacology, 2001
- Mouse models of serotonin receptor function: toward a genetic dissection of serotonin systemsPharmacology & Therapeutics, 2000
- Role of Serotonin in the Paradoxical Calming Effect of Psychostimulants on HyperactivityScience, 1999
- Establishment of a noradrenergic clonal line of rat adrenal pheochromocytoma cells which respond to nerve growth factor.Proceedings of the National Academy of Sciences, 1976