Life without brain serotonin: Reevaluation of serotonin function with mice deficient in brain serotonin synthesis

•Tph2−/− mouse is an animal model depleted of the neurotransmitter serotonin.•In this review we critically discuss the recent data obtained from Tph2−/− mice.•We highlight the most robust phenotypes of this mouse model.•We suggest explanations for inconsistencies observed between different studies.

Tryptophan hydroxylase (TPH) is a rate limiting enzyme in the synthesis of serotonin (5-HT), a monoamine which works as an autacoid in the periphery and as a neurotransmitter in the central nervous system.In 2003 we have discovered the existence of a second Tph gene, which is expressed exclusively in the brain, and, therefore, is responsible for the 5-HT synthesis in the central nervous system. In the following years several research groups have independently generated Tph2-deficient mice. In this review we will summarize the data gained from the existing mouse models with constitutive or conditional deletion of the Tph2 gene, focusing on biochemical, developmental, and behavioral consequences of Tph2-deficiency.