title: Generation of Pet1210-Cre transgenic mouse line reveals non-serotonergic expression domains of Pet1 both in CNS and periphery.
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.
authors.affiliation: Department of Biology, Unit of Cell and Developmental Biology, University of Pisa, Pisa, Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: Pelosi
authors.affiliation: Department of Biology, Unit of Cell and Developmental Biology, University of Pisa, Pisa, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Migliarini
authors.affiliation: Department of Biology, Unit of Cell and Developmental Biology, University of Pisa, Pisa, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Pacini
authors.affiliation: Department of Biology, Unit of Cell and Developmental Biology, University of Pisa, Pisa, Italy.
authors.forename: Marta
authors.initials: M
authors.lastname: Pratelli
authors.affiliation: Department of Biology, Unit of Cell and Developmental Biology, University of Pisa, Pisa, Italy; Istituto Italiano di Tecnologia, Center for Neuroscience and Cognitive Systems @UniTn, Rovereto, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Pasqualetti
mesh_terms: D000818:Animals; D019070:Cell Lineage; D002490:Central Nervous System / Q000196:embryology*; D018507:Gene Expression Regulation, Developmental; D000090322:Homeobox Protein Nkx-2.2; D019426:Integrases / Q000096:biosynthesis* / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D009928:Organ Specificity / Q000235:genetics; D017434:Protein Structure, Tertiary; D012701:Serotonin / Q000235:genetics / Q000378:metabolism*; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000096:biosynthesis* / Q000235:genetics; D014365:Tryptophan Hydroxylase / Q000235:genetics / Q000378:metabolism
chemical_list: C484684:Fev protein, mouse; D000090322:Homeobox Protein Nkx-2.2; C000715627:Nkx2-2 protein, mouse; D050486:Serotonin Plasma Membrane Transport Proteins; C493231:Slc6a4 protein, mouse; D014157:Transcription Factors; D012701:Serotonin; C487802:Tph2 protein, mouse; D014365:Tryptophan Hydroxylase; C045073:Cre recombinase; D019426:Integrases
references.citation: Cancer Genet Cytogenet. 2009 Oct;194(1):53-7
references.pmid: 19737655
references.citation: Neuropsychopharmacology. 2003 Feb;28(2):206-15
references.pmid: 12589373
references.citation: Brain Res Bull. 2001 Nov 15;56(5):479-85
references.pmid: 11750793
references.citation: Acta Physiol Scand Suppl. 1964;:SUPPL 232:1-55
references.pmid: 14229500
references.citation: J Neurosci. 2002 Jul 1;22(13):5442-51
references.pmid: 12097496
references.citation: Neuroscience. 2004;124(3):573-81
references.pmid: 14980728
references.citation: Genomics. 1998 Aug 1;51(3):445-51
references.pmid: 9721215
references.citation: Nature. 1993 Mar 18;362(6417):258-61
references.pmid: 8459851
references.citation: Nat Genet. 2000 Jun;25(2):139-40
references.pmid: 10835623
references.citation: Nat Genet. 1998 May;19(1):47-50
references.pmid: 9590287
references.citation: Development. 2009 Jul;136(14):2477-85
references.pmid: 19542360
references.citation: Nat Neurosci. 2013 Aug;16(8):1016-23
references.pmid: 23852112
references.citation: Nat Genet. 2003 Sep;35(1):70-5
references.pmid: 12923530
references.citation: Oncogene. 1997 Mar 13;14(10):1159-64
references.pmid: 9121764
references.citation: PLoS One. 2011 Jan 05;6(1):e15998
references.pmid: 21246047
references.citation: J Neurosci Methods. 2005 Apr 15;143(1):27-32
references.pmid: 15763133
references.citation: Ann Med. 1999 Feb;31(1):12-33
references.pmid: 10219711
references.citation: J Neurosci. 2005 Mar 9;25(10):2628-36
references.pmid: 15758173
references.citation: J Am Soc Nephrol. 2005 Jul;16(7):1993-2002
references.pmid: 15917337
references.citation: Nat Rev Genet. 2001 Oct;2(10):769-79
references.pmid: 11584293
references.citation: Experientia. 1964 Jul 15;20(7):398-9
references.pmid: 5856530
references.citation: Am J Hum Genet. 1998 Dec;63(6):1651-8
references.pmid: 9837817
references.citation: Nat Rev Neurosci. 2003 Dec;4(12):1002-12
references.pmid: 14618156
references.citation: Mol Psychiatry. 2007 Apr;12(4):331-59
references.pmid: 17389902
references.citation: Nat Genet. 1998 May;19(1):51-5
references.pmid: 9590288
references.citation: Proc Natl Acad Sci U S A. 2007 Jan 2;104(1):329-34
references.pmid: 17182745
references.citation: Mol Psychiatry. 2009 Mar;14(3):280-90
references.pmid: 18663366
references.citation: J Neurosci. 1999 Dec 1;19(23):10348-56
references.pmid: 10575032
references.citation: Dev Genes Evol. 2002 Feb;212(1):43-6
references.pmid: 11875656
references.citation: Genesis. 2001 Sep;31(1):37-42
references.pmid: 11668676
references.citation: J Comp Neurol. 1982 May 20;207(3):239-54
references.pmid: 7107985
references.citation: Nat Neurosci. 2010 Oct;13(10):1190-8
references.pmid: 20818386
references.citation: Neuropharmacology. 2008 Nov;55(6):994-1005
references.pmid: 18789954
references.citation: Mol Psychiatry. 2013 Oct;18(10):1106-18
references.pmid: 23007167
references.citation: Int Rev Neurobiol. 2004;59:111-74
references.pmid: 15006487
references.citation: Neuroscience. 1982 Apr;7(4):951-75
references.pmid: 7048127
references.citation: Genomics. 2001 Apr 1;73(1):56-65
references.pmid: 11352566
references.citation: Gene. 1989 Apr 15;77(1):61-8
references.pmid: 2744488
references.citation: Transgenic Res. 2001 Apr;10(2):83-103
references.pmid: 11305364
references.citation: Neuropeptides. 2005 Feb;39(1):1-8
references.pmid: 15627494
references.citation: Physiol Behav. 2004 Nov 15;83(2):291-307
references.pmid: 15488546
references.citation: J Neurobiol. 1998 Feb 5;34(2):151-63
references.pmid: 9468386
references.citation: Clin Cancer Res. 2009 Apr 15;15(8):2747-55
references.pmid: 19336516
references.citation: Eur J Neurosci. 2011 Nov;34(10):1553-62
references.pmid: 22103413
references.citation: Genes Dev. 2003 Mar 15;17(6):729-37
references.pmid: 12651891
references.citation: Nat Neurosci. 2004 Jun;7(6):589-95
references.pmid: 15133515
references.citation: Diabetes. 2011 Dec;60(12):3208-16
references.pmid: 22013016
references.citation: J Comp Neurol. 2012 Dec 15;520(18):4157-67
references.pmid: 22605640
references.citation: Eur J Neurosci. 2012 Jan;35(1):85-96
references.pmid: 22151329
references.citation: J Comp Neurol. 2004 Jan 19;468(4):518-29
references.pmid: 14689484
references.citation: Brain Res Bull. 1982 Jul-Dec;9(1-6):559-604
references.pmid: 6756556
references.citation: Nat Genet. 1999 Jan;21(1):70-1
references.pmid: 9916792
references.citation: Nature. 2011 Apr 21;472(7343):347-50
references.pmid: 21512572
references.citation: ACS Chem Neurosci. 2013 Jan 16;4(1):22-5
references.pmid: 23336040
references.citation: BMC Dev Biol. 2001;1:4
references.pmid: 11299042
references.citation: Nat Neurosci. 2008 Apr;11(4):417-9
references.pmid: 18344997
references.citation: Nat Rev Neurosci. 2001 Dec;2(12):861-70
references.pmid: 11733793
references.citation: Nature. 2003 Oct 30;425(6961):917-25
references.pmid: 14586460
references.citation: Brain Res Bull. 1983 Apr;10(4):459-79
references.pmid: 6344960
references.citation: J Chem Neuroanat. 2011 Jul;41(4):247-55
references.pmid: 21550397
references.citation: Proc Natl Acad Sci U S A. 2005 Nov 8;102(45):16472-7
references.pmid: 16251278
references.citation: Methods Mol Biol. 2014;1092:437-54
references.pmid: 24318835
references.citation: J Neurosci. 2003 Nov 5;23(31):9961-7
references.pmid: 14602809
references.citation: Neuropharmacology. 2011 Sep;61(3):524-43
references.pmid: 21530552
references.citation: J Mol Diagn. 2007 Sep;9(4):459-63
references.pmid: 17620387
references.citation: Neuroscience. 2006 Jul 7;140(3):1067-77
references.pmid: 16600519
references.citation: J Clin Invest. 2002 Apr;109(8):1073-82
references.pmid: 11956245
references.citation: Nat Neurosci. 2003 Sep;6(9):933-8
references.pmid: 12897786
references.citation: Front Mol Neurosci. 2009 Nov 06;2:24
references.pmid: 19936315
references.citation: Novartis Found Symp. 2005;268:171-83; discussion 183-9, 242-53
references.pmid: 16206880