title: Targeted insertion of the Cre-recombinase gene at the phenylethanolamine n-methyltransferase locus: a new model for studying the developmental distribution of adrenergic cells.
abstract: To evaluate the developmental distribution of adrenergic cells in vivo, we inserted the Cre-recombinase gene into the locus encoding for the epinephrine biosynthetic enzyme phenylethanolamine n-methyltransferase (Pnmt) and crossed these Pnmt-Cre mice with ROSA26 reporter (R26R) mice to activate LacZ (encoding beta-galactosidase) expression in cells that were selectively derived from the adrenergic lineage. Our data show the following: (1) Insertion of Cre-recombinase into the Pnmt locus created a functional knockout of Pnmt expression with concomitant loss of epinephrine in homozygous Pnmt(Cre/Cre) mice; (2) Despite the reduction in Pnmt expression and epinephrine production in Pnmt(Cre/Cre) mice, these mice were viable and fertile, with no apparent developmental defects; (3) When crossed with R26R mice, Pnmt-Cre activation of LacZ expression faithfully recapitulated Pnmt expression in vivo; and (4) LacZ expression was activated in substantial numbers of pacemaking, conduction, and working cardiomyocytes.
authors.affiliation: Department of Pharmacology, Georgetown University Medical Center, Washington, DC 20057, USA. eberts@georgetown.edu
authors.forename: Steven N
authors.initials: SN
authors.lastname: Ebert
authors.forename: Qi
authors.initials: Q
authors.lastname: Rong
authors.forename: Steven
authors.initials: S
authors.lastname: Boe
authors.forename: Robert P
authors.initials: RP
authors.lastname: Thompson
authors.forename: Alexander
authors.initials: A
authors.lastname: Grinberg
authors.forename: Karl
authors.initials: K
authors.lastname: Pfeifer
mesh_terms: D000311:Adrenal Glands / Q000166:cytology / Q000196:embryology* / Q000502:physiology; D000818:Animals; D004837:Epinephrine / Q000502:physiology*; D005260:Female; D018507:Gene Expression Regulation, Developmental; D015971:Gene Expression Regulation, Enzymologic; D017930:Genes, Reporter; D019426:Integrases / Q000235:genetics*; D007763:Lac Operon; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D023421:Models, Animal; D016254:Mutagenesis, Insertional; D010625:Phenylethanolamine N-Methyltransferase / Q000235:genetics*; D011247:Pregnancy
chemical_list: D010625:Phenylethanolamine N-Methyltransferase; C045073:Cre recombinase; D019426:Integrases; D004837:Epinephrine