Conditional knockout mouse for tissue-specific disruption of the cyclooxygenase-2 (Cox-2) gene

被引:45
作者
Ishikawa, T
Herschman, HR
机构
[1] Univ Calif Los Angeles, Dept Biol Chem, Dept Mol & Med Pharmacol, Los Angeles, CA 90095 USA
[2] Univ Calif Los Angeles, Inst Mol Biol, David Geffen Sch Med, Los Angeles, CA 90095 USA
关键词
gene targeting; conditional knockout; cyclooxygenase; Cox-2; Cre-loxP;
D O I
10.1002/gene.20192
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
Cyclooxygenase-2 (Cox-2) modulates many normal functions, and appears to play a role in a wide variety of pathophysiologic conditions. Cox-2 gene expression is induced in many different cell types, in response to many distinct stimuli. We generated a conditional knockout mouse in which critical exons of the Cox-2 gene are flanked with IoxP sites. Cox-2(flox/flox) mice appear normal and are fertile. Recombination at the IoxP sites, loss of Cox-2 protein expression, and prevention of induced PGE2 accumulation are observed in Cox-2(flox/flox) mouse embryo fibroblasts following infection with an adenovirus expressing CRE recombinase. In vivo recombination at the Cox-2(flox) allele was demonstrated in the liver of Cox-2(flox)/(flox) mice following intravenous injection of adenovirus expressing CRE recombinase. Spatially and temporally restricted elimination of the Cox-2 gene in Cox-2(flox/flox) conditional knockout mice should provide a valuable tool to analyze the cell type-specific role of Cox-2 in many disease models.
引用
收藏
页码:143 / 149
页数:7
相关论文
共 22 条
[1]  
[Anonymous], 1994, MANIPULATING MOUSE E
[2]  
Chulada PC, 2000, CANCER RES, V60, P4705
[3]   RENAL ABNORMALITIES AND AN ALTERED INFLAMMATORY RESPONSE IN MICE LACKING CYCLOOXYGENASE-II [J].
DINCHUK, JE ;
CAR, BD ;
FOCHT, RJ ;
JOHNSTON, JJ ;
JAFFEE, BD ;
COVINGTON, MB ;
CONTEL, NR ;
ENG, VM ;
COLLINS, RJ ;
CZERNIAK, PM ;
GORRY, SA ;
TRZASKOS, JM .
NATURE, 1995, 378 (6555) :406-409
[4]  
Herschman Harvey R, 2003, Mol Imaging Biol, V5, P286
[5]  
Herschman HR, 2002, CANC DRUG DISC DEV, P13
[6]  
HERSCHMAN HR, 2004, EICOSANOIDS
[7]   ADENOVIRUS-MEDIATED TRANSFER OF LOW-DENSITY-LIPOPROTEIN RECEPTOR GENE ACUTELY ACCELERATES CHOLESTEROL CLEARANCE IN NORMAL MICE [J].
HERZ, J ;
GERARD, RD .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1993, 90 (07) :2812-2816
[8]   Requirement for tumor suppressor Apc in the morphogenesis of anterior and ventral mouse embryo [J].
Ishikawa, T ;
Tamai, Y ;
Li, Q ;
Oshima, M ;
Taketo, MM .
DEVELOPMENTAL BIOLOGY, 2003, 253 (02) :230-246
[9]  
ISHIKAWA T, 2006, IN PRESS MOL IMAGING
[10]  
KUJUBU DA, 1991, J BIOL CHEM, V266, P12866