Only low levels of exogenous N-acetyltransferase can be achieved in transgenic mice

被引:17
作者
Cao, W
Chau, B
Hunter, R
Strnatka, D
McQueen, CA
Erickson, RP
机构
[1] Univ Arizona, Dept Pediat, Coll Med, Tucson, AZ 85724 USA
[2] Univ Arizona, Dept Pediat, Coll Pharm, Tucson, AZ 85724 USA
[3] Univ Arizona, Dept Pharmacol, Coll Med, Tucson, AZ 85724 USA
[4] Univ Arizona, Dept Pharmacol, Coll Pharm, Tucson, AZ 85724 USA
[5] Univ Arizona, Dept Mol & Cellular Biol, Coll Sci, Tucson, AZ 85721 USA
关键词
transgenics; N-acetyltransferase; folates; aromatic amines; gene regulation;
D O I
10.1038/sj.tpj.6500319
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
Therapeutic and environmental aromatic amines and hydrazines are substrates for the arylamine N-acetyltransferases (NAT). In all, 10 transgenic lines containing either the human NAT1 or NAT2 transgene were developed using multiple promoters. The presence of the transgene was confirmed by determining copy number, mRNA and enzyme activity. Despite some lines having high copy numbers of the transgene, only modest or no increases in enzymatic activity could be found in a variety of tissues. The NAT1 transgene could not be bred to homozygosity. The cytomegalovirus (CMV)-promoted NAT1 transgene increased endogenous Nat1 mRNA levels in liver and had little effect on endogenous Nat2 mRNA levels. The presence of the CMV-promoted NAT2 transgene appeared to suppress endogenous hepatic Nat2 mRNA, but did not alter Nat1 mRNA levels. The failure to achieve high expression of any of the transgenes suggests that overexpression of NAT genes may have harmful effects during development.
引用
收藏
页码:255 / 261
页数:7
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