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

TitleGeneration and analysis of mice with a targeted disruption of the arylamine N-acetyltransferase type 2 gene.
Publication TypeJournal Article
Year of Publication2003
AuthorsCornish VA, Pinter K, Boukouvala S, Johnson N, Labrousse C, Payton M, Priddle H, Smith AG, Sim E
JournalPharmacogenomics J
Volume3
Issue3
Pagination169-77
Date Published2003
ISSN1470-269X
KeywordsAmino Acid Transport System A, Amino Acid Transport Systems, Animals, Carrier Proteins, Crosses, Genetic, Female, Gene Targeting, Inbreeding, Liver, Male, Mice, Mice, Inbred A, Mice, Inbred C57BL, Mice, Knockout
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.

DOI10.1038/sj.tpj.6500170
Alternate JournalPharmacogenomics J.
PubMed ID12815365