Generation of Pet1210-Cre transgenic mouse line reveals non-serotonergic expression domains of Pet1 both in CNS and periphery

PLoS One. 2014 Aug 6;9(8):e104318. doi: 10.1371/journal.pone.0104318. eCollection 2014.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Lineage*
  • Central Nervous System / embryology*
  • Gene Expression Regulation, Developmental*
  • Integrases / biosynthesis*
  • Integrases / genetics
  • Mice
  • Mice, Transgenic
  • Organ Specificity / genetics
  • Protein Structure, Tertiary
  • Serotonin / genetics
  • Serotonin / metabolism*
  • Serotonin Plasma Membrane Transport Proteins / genetics
  • Serotonin Plasma Membrane Transport Proteins / metabolism
  • Transcription Factors / biosynthesis*
  • Transcription Factors / genetics
  • Tryptophan Hydroxylase / genetics
  • Tryptophan Hydroxylase / metabolism

Substances

  • Fev protein, mouse
  • Serotonin Plasma Membrane Transport Proteins
  • Slc6a4 protein, mouse
  • Transcription Factors
  • Serotonin
  • Tph2 protein, mouse
  • Tryptophan Hydroxylase
  • Cre recombinase
  • Integrases

Grant support

This work was supported by the Italian Ministry of Education, University and Research (MIUR) (Prin 2008, 200894SYW2) and Toscana Life Sciences Foundation (Orphan_0108 program) to MP. BP and GP were supported by a PhD program from the University of Pisa. SM was supported by the Regional Program and European Social Fund. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.