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Deficiency of brain 5-HT synthesis but serotonergic neuron formation in Tph2 knockout mice

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The relative contribution of the two tryptophan hydroxylase (TPH) isoforms, TPH1 and TPH2, to brain serotonergic system function is controversial. To investigate the respective role of TPH2 in neuron serotonin (5-HT) synthesis and the role of 5-HT in brain development, mice with a targeted disruption of Tph2 were generated. The preliminary results indicate that in Tph2 knockout mice raphe neurons are completely devoid of 5-HT, whereas no obvious alteration in morphology and fiber distribution are observed. The findings confirm the exclusive specificity of Tph2 in brain 5-HT synthesis and suggest that Tph2-synthesized 5-HT is not required for serotonergic neuron formation.

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The authors are grateful to S. Wiese for providing cloning vectors and construct advise as well as to M. Sendtner, C. Gross and P. Gaspar for helpful discussions and continuing support. The authors also thank N. Steigerwald for the genotyping of mice and H. Brunner for expertise in animal husbandry. This research is supported by the Deutsche Forschungsgemeinschaft (SFB 581; KFO 125; GRK 1253 fellowship to C·K., GSLS fellowship to J.W.), European Commission (NEWMOOD LSHMCT-2003-503474), and the Bundesministerium für Bildung und Forschung (IZKF 01 KS 9603).

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Correspondence to Lise Gutknecht or Klaus-Peter Lesch.

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Gutknecht, L., Waider, J., Kraft, S. et al. Deficiency of brain 5-HT synthesis but serotonergic neuron formation in Tph2 knockout mice. J Neural Transm 115, 1127–1132 (2008).

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