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

The Pharmacogenomics Journal volume 5, pages 255–261 (2005)Cite this article

Abstract

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.

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Acknowledgements

We thank Drs Gerald Levy and Wendell Weber of the Department of Pharmacology and Dr Kotoku Kurachi, Department of Human Genetics, of the University of Michigan, for constructs and Ms Donelle Myers for secretarial help. This work was supported by ES10047 to CAM and the Genetically Modified Mouse Service, funded by CA23074 and ES06694.

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  1. W Cao

    Present address: Department of Clinical Pharmacology, Jinling Hospital, 305 E Zhongshan Road, Nanjing, Jiangsu Province, 210002, People's Republic of China

Authors and Affiliations

  1. Department of Pediatrics, Colleges of Medicine and Pharmacy, University of Arizona, Tucson, AZ, USA

    W Cao, R Hunter, D Strnatka & R P Erickson

  2. Department of Pharmacology and Toxicology, Colleges of Medicine and Pharmacy, University of Arizona, Tucson, AZ, USA

    B Chau & C A McQueen

  3. Department of Molecular and Cellular Biology, College of Science, University of Arizona, Tucson, AZ, USA

    R P Erickson

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Correspondence to R P Erickson.

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Cao, W., Chau, B., Hunter, R. et al. Only low levels of exogenous N-acetyltransferase can be achieved in transgenic mice. Pharmacogenomics J 5, 255–261 (2005). https://doi.org/10.1038/sj.tpj.6500319

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