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  • Title: Tryptophan hydroxylase-2 controls brain serotonin synthesis.
    Author: Zhang X, Beaulieu JM, Sotnikova TD, Gainetdinov RR, Caron MG.
    Journal: Science; 2004 Jul 09; 305(5681):217. PubMed ID: 15247473.
    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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