Genetically modified animals in pharmacological research:: future trends

被引:16
作者
Rudolph, U
Möhler, H
机构
[1] Univ Zurich, Inst Pharmacol, CH-8057 Zurich, Switzerland
[2] Swiss Fed Inst Technol, Inst Pharmacol, Zurich, Switzerland
关键词
transgenic; gene targeting; gene knockout; mutagenesis; tetracycline; inducible gene expression;
D O I
10.1016/S0014-2999(99)00195-8
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
The recognition of molecular control elements which govern cell and organ function is essential for the development of novel drug therapies and for an understanding of drug actions. Thus, a major interest is focused on methodologies which permit the identification of novel control elements. This is of particular relevance for the identification of drug targets, the distinction of target isoforms, the differentiation of signalling pathways, the generation of disease models and toxicological testing. In this review, we discuss different classes of genetically modified animals and their potential to elucidate biological processes relevant for pharmacological research including functional genomics. Techniques which permit the time- and tissue-specific inducible regulation of gene expression present an important methodological advance. (C) 1999 Elsevier Science B.V. All rights reserved.
引用
收藏
页码:327 / 337
页数:11
相关论文
共 75 条
[1]   NONINVASIVE LIPOSOME-MEDIATED GENE DELIVERY CAN CORRECT THE ION-TRANSPORT DEFECT IN CYSTIC-FIBROSIS MUTANT MICE [J].
ALTON, EWFW ;
MIDDLETON, PG ;
CAPLEN, NJ ;
SMITH, SN ;
STEEL, DM ;
MUNKONGE, FM ;
JEFFERY, PK ;
GEDDES, DM ;
HART, SL ;
WILLIAMSON, R ;
FASOLD, KI ;
MILLER, AD ;
DICKINSON, P ;
STEVENSON, BJ ;
MCLACHLAN, G ;
DORIN, JR ;
PORTEOUS, DJ .
NATURE GENETICS, 1993, 5 (02) :135-142
[2]   Functional identification of the mouse circadian Clock gene by transgenic BAC rescue [J].
Antoch, MP ;
Song, EJ ;
Chang, AM ;
Vitaterna, MH ;
Zhao, YL ;
Wilsbacher, LD ;
Sangoram, AM ;
King, DP ;
Pinto, LH ;
Takahashi, JS .
CELL, 1997, 89 (04) :655-667
[3]   Generation of conditional mutants in higher eukaryotes by switching between the expression of two genes [J].
Baron, U ;
Schnappinger, D ;
Helbl, V ;
Gossen, M ;
Hillen, W ;
Bujard, H .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1999, 96 (03) :1013-1018
[4]   Pharmacology of recombinant γ-aminobutyric acida receptors rendered diazepam-insensitive by point-mutated α-subunits [J].
Benson, JA ;
Löw, K ;
Keist, R ;
Mohler, H ;
Rudolph, U .
FEBS LETTERS, 1998, 431 (03) :400-404
[5]   Different thermostabilities of FLP and Cre recombinases: Implications for applied site-specific recombination [J].
Buchholz, F ;
Ringrose, L ;
Angrand, PO ;
Rossi, F ;
Stewart, AF .
NUCLEIC ACIDS RESEARCH, 1996, 24 (21) :4256-4262
[6]   Improved properties of FLP recombinase evolved by cycling mutagenesis [J].
Buchholz, F ;
Angrand, PO ;
Stewart, AF .
NATURE BIOTECHNOLOGY, 1998, 16 (07) :657-662
[7]  
BURKI K, 1995, ADV DRUG RES, V26, P143
[8]   MICE DEFICIENT FOR P53 ARE DEVELOPMENTALLY NORMAL BUT SUSCEPTIBLE TO SPONTANEOUS TUMORS [J].
DONEHOWER, LA ;
HARVEY, M ;
SLAGLE, BL ;
MCARTHUR, MJ ;
MONTGOMERY, CA ;
BUTEL, JS ;
BRADLEY, A .
NATURE, 1992, 356 (6366) :215-221
[9]   Using Flp-recombinase to characterize expansion of Wnt1-expressing neural progenitors in the mouse [J].
Dymecki, SM ;
Tomasiewicz, H .
DEVELOPMENTAL BIOLOGY, 1998, 201 (01) :57-65
[10]   Flp recombinase promotes site-specific DNA recombination in embryonic stem cells and transgenic mice [J].
Dymecki, SM .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1996, 93 (12) :6191-6196