A tryptophan hydroxlyase 1 reporter that directs Cre recombinase extinguishable placental alkaline phosphatase expression in serotonergic (5-HT) neurons and peripheral tissues

The serotonergic (5-HT) system modulates many behaviors and has been implicated in psychiatric disorders, but the density of 5-HT processes has complicated analyses. We have used regulatory regions from the Tryptophan hydroxylase 1 (Tph1) gene to drive expression of LoxP-flanked placental alkaline phosphatase (PLAP) to generate the Tph1-Lox-PLAP reporter mouse line. In these mice, PLAP is expressed in the hindbrain raphe nuclei and in peripheral tissues known to express Tph1. Tph1 is expressed at low levels in neurons. While, in Tph1-Lox-PLAP mice, most PLAP-expressing neurons are monoaminergic, PLAP was expressed in only 5-10% of neurons expressing the predominant neuronal 5-HT biosynthetic enzyme Tph2, serotonin transporter (SERT) or aromatic amino acid decarboxylase (AADC). To test this reporter further, we examined the brains of mice carrying the anorexia (anx) mutation, in which increased overall density of 5-HT immunoreactivity had been previously observed at P21. PLAP-labeling of processes in anx/anx and anx/+ mice was reduced at P0. By P10, distribution of PLAP-labeled processes in anx/+ and +/+ cortices was indistinguishable, but differed markedly from that seen in the cortical layers of anx/anx mice. Thus, the Tph1-LoxP-PLAP reporter revealed a dosage sensitive role of the anx mutation in the early 5-HT system and later cortical layer-specific differences in 5-HT process distribution in anx/anx mice. Thus, the Tph1-LoxP-PLAP reporter provides a sensitive indicator for analyses of serotonergic cells in the brain and periphery.