TARGETED DISRUPTION OF THE MOUSE B-2 BRADYKININ RECEPTOR IN EMBRYONIC STEM-CELLS

被引：10

作者：

BORKOWSKI, JA ^{[1
]}

HESS, JF ^{[1
]}

机构：

[1] MERCK & CO INC,MERCK SHARP & DOHME RES LABS,DEPT MOLEC PHARMACOL & BIOCHEM,RAHWAY,NJ 07065

来源：

CANADIAN JOURNAL OF PHYSIOLOGY AND PHARMACOLOGY | 1995年 / 73卷 / 07期

关键词：

BRADYKININ; G-PROTEIN-COUPLED RECEPTOR; EMBRYONIC STEM CELLS; GENE TARGETING; HOMOLOGOUS; RECOMBINATION;

D O I：

10.1139/y95-104

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Two mammalian genes encoding bradykinin (BK) receptors termed B-1 and B-2 have been identified by molecular cloning techniques. Some pharmacological data suggest the existence of further subtypes of the B-2 receptor. To unambiguously determine whether additional genes encoding B-2 BK receptors might exist in mammals, steps have been taken toward the generation of mice with a ''knockout'' of the BK B-2 receptor. A genomic clone of the mouse B-2 BK receptor was isolated and its coding sequence determined by DNA sequence analysis. A physical map of the DNA flanking this coding sequence was generated. A vector, pBS-KO-1, was constructed for targeted disruption of the mouse B-2 receptor gene. This vector contains 1 kb (kilobase) of DNA upstream of the mouse B-2 receptor coding sequence, a neomycin resistance gene (neo), and 5.4 kb of DNA downstream of the B-2 receptor coding sequence. Thus, the correct homologous recombination event will result in a chromosome in which the coding sequence for the mouse B-2 BK receptor is replaced with the neomycin resistance gene. pBS-KO-1 was transfected into embryonic stem cells, and clones containing a targeted disruption of the mouse B-2 BK receptor were identified.

引用

页码：773 / 779

页数：7

共 33 条

[1] BRADYKININ ANALOGS - DIFFERENTIAL AGONIST AND ANTAGONIST ACTIVITIES SUGGESTING MULTIPLE RECEPTORS [J].

BRAAS, KM ;

MANNING, DC ;

PERRY, DC ;

SNYDER, SH .

BRITISH JOURNAL OF PHARMACOLOGY, 1988, 94 (01) :3-5

[2] FORMATION OF GERM-LINE CHIMERAS FROM EMBRYO-DERIVED TERATOCARCINOMA CELL-LINES [J].

BRADLEY, A ;

EVANS, M ;

KAUFMAN, MH ;

ROBERTSON, E .

NATURE, 1984, 309 (5965) :255-256

[3] RECENT DEVELOPMENTS IN THE UNDERSTANDING OF BRADYKININ RECEPTORS [J].

BURCH, RM ;

KYLE, DJ .

LIFE SCIENCES, 1992, 50 (12) :829-838

[4] ALTERING THE GENOME BY HOMOLOGOUS RECOMBINATION [J].

CAPECCHI, MR .

SCIENCE, 1989, 244 (4910) :1288-1292

[5]

CONKLIN BR, 1988, J PHARMACOL EXP THER, V244, P646

[6]

DENNING GM, 1991, J BIOL CHEM, V266, P12932

[7] BRADYKININ AND INFLAMMATORY PAIN [J].

DRAY, A ;

PERKINS, M .

TRENDS IN NEUROSCIENCES, 1993, 16 (03) :99-104

[8] MOLECULAR-CLONING, FUNCTIONAL EXPRESSION AND PHARMACOLOGICAL CHARACTERIZATION OF A HUMAN BRADYKININ-B2 RECEPTOR GENE [J].

EGGERICKX, D ;

RASPE, E ;

BERTRAND, D ;

VASSART, G ;

PARMENTIER, M .

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1992, 187 (03) :1306-1313

[9] HIGH-EFFICIENCY VECTORS FOR COSMID MICROCLONING AND GENOMIC ANALYSIS [J].

EVANS, GA ;

LEWIS, K ;

ROTHENBERG, BE .

GENE, 1989, 79 (01) :9-20

[10]

FARMER SG, 1989, MOL PHARMACOL, V36, P1

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