Brain-specific conditional and time-specific inducible Tph2 knockout mice possess normal serotonergic gene expression in the absence of serotonin during adult life.

Several lines of evidence implicate a dysregulation of tryptophan hydroxylase (TPH)-dependent serotonin (5-HT) synthesis in emotional behaviour and stress, and point to its relevance for the etiology and pathogenesis of various neuropsychiatric disorders. We therefore studied different animal models featuring reduced Tph2 expression to investigate the consequences of impaired brain 5-HT synthesis on neuronal development. Specifically, brain-specific conditional and time-specific inducible Tph2 knockout (KO) models were generated and investigated for altered serotonergic neuron-specific gene expression.

The expression of the transcription factor FEV in adult human brain and its association with affective disorders.

A wide range of physiological processes and neuronal functioning is modulated by the serotonergic system. Serotonin (5-HT) plays an important role during early brain development. Moreover, dysfunction of the 5-HT system is implicated in psychiatric disorders, especially in affective disorders.

Spatio-temporal expression of tryptophan hydroxylase isoforms in murine and human brain: convergent data from Tph2 knockout mice.

Dysregulation of tryptophan hydroxylase (TPH)-dependent serotonin (5-HT) synthesis, has been implicated in various neuropsychiatric disorders, although the differential expression pattern of the two isoforms is controversial. Here, we report a comprehensive spatio-temporal isoform-specific analysis of TPH1 and TPH2 expression during pre- and postnatal development of mouse brain and in adult human brain. TPH2 expression was consistently detected in the raphe nuclei, as well as in fibers in the deep pineal gland and in small intestine.

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

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.

Tryptophan hydroxylase-2 gene variation influences personality traits and disorders related to emotional dysregulation.

Variation in the tryptophan hydroxylase-2 gene (TPH2) coding for the rate-limiting enzyme of serotonin (5-HT) synthesis in the brain modulates responses of limbic circuits to emotional stimuli and has been linked to a spectrum of clinical populations characterized by emotional dysregulation. Here, we tested a set of common single nucleotide polymorphisms (SNPs) in and downstream of the transcriptional control region of TPH2 for association with personality traits and with risk for personality disorders in two cohorts comprising of 336 healthy individuals and 420 patients with personality disorders. Personality dimensions were assessed by the Tridimensional Personality Questionnaire (TPQ) and the revised NEO Personality Inventory (NEO-PI-R).