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Generation and analysis of mice with a targeted disruption of the arylamine N-acetyltransferase type 2 gene

ABSTRACT

Arylamine N-acetyltransferases (NATs) are polymorphic xenobiotic metabolising enzymes, linked to cancer susceptibility in a variety of tissues. In humans and in mice there are multiple NAT isoforms. To identify whether the different isoforms represent inbuilt redundancy or whether they have unique roles, we have generated mice with a null allele of Nat2 by gene targeting. This mouse line conclusively demonstrates that the different isoforms have distinct functions with no compensatory expression in the Nat2 null animals of the other isoforms. In addition, we have used the transgenic line to show the pattern of Nat2 expression during development. Although Nat2 is not essential for embryonic development, it has a widespread tissue distribution from at least embryonic day 9.5. This mouse line now paves the way for the teratological role of Nat2 to be tested.

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Abbreviations

CL/P:

cleft lip with or without cleft palate

NAT:

arylamine N-acetyltransferase

NTD:

neural tube defect

p-aba:

para-aminobenzoic acid

p-abaglu:

para-aminobenzoylglutamate

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Acknowledgements

We thank Chris Denning for isolation and characterisation of the lambda genomic clones, Lorraine Dobbie and Daniella Nebenius-Oosthuizen for generation of the two knockout chimeras, Diana Peddie for breeding and along with Mimi Mo and Naila Khodabukus for genotyping of the transgenic mice, Peter Busby for animal husbandry, Robert Erickson and Charlene McQueen for helpful discussions and John Sinclair for help with the generation of antiserum 185. The ISCR (formerly Centre for Genome Research) Gene Targeting Lab was funded by the UK Biotechnology and Biological Sciences Research Council. The work in Oxford was supported by grants from The Wellcome Trust and Action Research.

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Cornish, V., Pinter, K., Boukouvala, S. et al. Generation and analysis of mice with a targeted disruption of the arylamine N-acetyltransferase type 2 gene. Pharmacogenomics J 3, 169–177 (2003). https://doi.org/10.1038/sj.tpj.6500170

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