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. 2004 Jul 9;305(5681):217.
doi: 10.1126/science.1097540.

Tryptophan hydroxylase-2 controls brain serotonin synthesis

Xiaodong Zhang  1 , Jean-Martin Beaulieu, Tatyana D Sotnikova, Raul R Gainetdinov, Marc G Caron
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Tryptophan hydroxylase-2 controls brain serotonin synthesis

Xiaodong Zhang et al. Science. .

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.

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