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Science 9 July 2004:
Vol. 305. no. 5681, p. 217
DOI: 10.1126/science.1097540
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Tryptophan Hydroxylase-2 Controls Brain Serotonin Synthesis

Xiaodong Zhang, Jean-Martin Beaulieu, Tatyana D. Sotnikova, Raul R. Gainetdinov, Marc G. Caron*

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.

Howard Hughes Medical Institute Laboratory, Department of Cell Biology, and Center for Models of Human Disease, Institute for Genome Sciences and Policy, Box 3287, Duke University Medical Center, Durham, NC 27710, USA.

* To whom correspondence should be addressed. E-mail: caron002{at}mc.duke.edu

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