Targeted insertion of the Cre-recombinase gene at the phenylethanolamine n-methyltransferase locus: A new model for studying the developmental distribution of adrenergic cells

被引:60
作者
Ebert, SN
Rong, Q
Boe, S
Thompson, RP
Grinberg, A
Pfeifer, K
机构
[1] Georgetown Univ, Ctr Med, Dept Pharmacol, Washington, DC 20057 USA
[2] NICHD, Lab Mammalian Genes & Dev, NIH, Bethesda, MD USA
[3] Med Univ S Carolina, Dept Cell Biol & Anat, Charleston, SC USA
关键词
epinephrine; catecholamines; pacemaking; heart development;
D O I
10.1002/dvdy.20188
中图分类号
R602 [外科病理学、解剖学]; R32 [人体形态学];
学科分类号
100101 ;
摘要
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 P-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. (C) 2004 Wiley-Liss, Inc.
引用
收藏
页码:849 / 858
页数:10
相关论文
共 32 条
[1]   MOLECULAR CONTROL OF CELL FATE IN THE NEURAL CREST - THE SYMPATHOADRENAL LINEAGE [J].
ANDERSON, DJ .
ANNUAL REVIEW OF NEUROSCIENCE, 1993, 16 :129-158
[2]   DISTRIBUTION OF DOPAMINE-CONTAINING, NORADRENALINE-CONTAINING, AND ADRENALINE-CONTAINING CELL-BODIES IN THE RAT MEDULLA-OBLONGATA - DEMONSTRATED BY THE IMMUNO-CYTOCHEMICAL LOCALIZATION OF CATECHOLAMINE BIOSYNTHETIC-ENZYMES [J].
ARMSTRONG, DM ;
ROSS, CA ;
PICKEL, VM ;
JOH, TH ;
REIS, DJ .
JOURNAL OF COMPARATIVE NEUROLOGY, 1982, 212 (02) :173-187
[3]   EXPRESSION AND DEVELOPMENT OF PHENYLETHANOLAMINE N-METHYLTRANSFERASE (PNMT) IN RAT-BRAIN STEM - STUDIES WITH GLUCOCORTICOIDS [J].
BOHN, MC ;
GOLDSTEIN, M ;
BLACK, IB .
DEVELOPMENTAL BIOLOGY, 1986, 114 (01) :180-193
[5]  
CLAYCOMB WC, 1976, J BIOL CHEM, V251, P6082
[6]   CARDIAC-MUSCLE HYPERTROPHY - DIFFERENTIATION AND GROWTH OF HEART CELL DURING DEVELOPMENT [J].
CLAYCOMB, WC .
BIOCHEMICAL JOURNAL, 1977, 168 (03) :599-601
[7]  
Cooper JR, 1991, BIOCH BASIS NEUROPHA, P220
[8]   THE DEVELOPMENT AND MATURATION OF ADRENAL-MEDULLARY CHROMAFFIN CELLS OF THE RAT INVIVO - A DESCRIPTIVE AND QUANTITATIVE STUDY [J].
COUPLAND, RE ;
TOMLINSON, A .
INTERNATIONAL JOURNAL OF DEVELOPMENTAL NEUROSCIENCE, 1989, 7 (05) :419-438
[9]  
DELACRUZ MV, 1977, J ANAT, V123, P661
[10]   Expression of phenylethanolamine N-methyltransferase in the embryonic rat heart [J].
Ebert, SN ;
Baden, JM ;
Mathers, LH ;
Siddall, BJ ;
Wong, DL .
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY, 1996, 28 (08) :1653-1658