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Neurons producing serotonin (5-hydroxytryptamine, 5-HT) constitute one of the most widely distributed neuronal networks in the mammalian central nervous system (CNS) and exhibit a profuse innervation throughout the CNS already at early stages of development. Serotonergic neuron specification is controlled by a combination of secreted molecules and transcription factors such as Shh, Fgf4/8, Nkx2.2, Lmx1b and Pet1. In the mouse,  Pet1  mRNA expression appears between 10 and 11  days post coitum ( dpc) in serotonergic post-mitotic precursors and persists in serotonergic neurons up to adulthood, where it promotes the expression of genes defining the mature serotonergic phenotype such as  tryptophan hydroxylase 2  ( Tph2 ) and  serotonin transporter  ( SERT ). Hence, the generation of genetic tools based on  Pet1  specific expression represents a valuable approach to study the development and function of the serotonergic system. Here, we report the generation of a  Pet1 210 -Cre  transgenic mouse line in which the  Cre recombinase  is expressed under the control of a 210 kb fragment from the  Pet1  genetic locus to ensure a reliable and faithful control of somatic recombination in  Pet1  cell lineage. Besides Cre-mediated recombination accurately occurred in the serotonergic system as expected and according to previous studies,  Pet1 210 -Cre  transgenic mouse line allowed us to identify novel, so far uncharacterized,  Pet1  expression domains. Indeed, we showed that in the  raphe Pet1  is expressed also in a non-serotonergic neuronal population intermingled with  Tph2 -expressing cells and mostly localized in the B8 and B9 nuclei. Moreover, we detected Cre-mediated recombination also in the developing pancreas and in the ureteric bud derivatives of the kidney, where it reflected a specific  Pet1  expression. Thus,  Pet1 210 -Cre  transgenic mouse line faithfully drives Cre-mediated recombination in all  Pet1  expression domains representing a valuable tool to genetically manipulate serotonergic and non-serotonergic  Pet1  cell lineages.

Generation of Pet1210-Cre Transgenic Mouse Line Reveals Non-Serotonergic Expression Domains of Pet1 Both in CNS and Periphery