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Publication : An N-ethyl-N-nitrosourea-induced mutation in N-acetyltransferase 1 in mice.

First Author  Erickson RP Year  2008
Journal  Biochem Biophys Res Commun Volume  370
Issue  2 Pages  285-8
PubMed ID  18373979 Mgi Jnum  J:134504
Mgi Id  MGI:3788986 Doi  10.1016/j.bbrc.2008.03.085
Citation  Erickson RP, et al. (2008) An N-ethyl-N-nitrosourea-induced mutation in N-acetyltransferase 1 in mice. Biochem Biophys Res Commun 370(2):285-8
abstractText  Genetic variation in human N-acetyltransferases (NAT) has been implicated in susceptibility to aromatic amine and hydrazine carcinogens and therapeutic drugs. There are mouse models for variability of human NAT1; however mice with genetic differences in Nat1 (corresponding to human NAT2), have not been available. N-Ethyl-N-nitrosourea (ENU) mutagenesis was used to create genetic variation in Nat1. Among a number of mutations identified, a base-pair change substituting threonine for isoleucine at position 95 was recovered and studied. Molecular models suggested that this substitution would alter substrate binding. Analysis of hepatic Nat1 activity with the selective substrate isoniazid showed that there was a significant reduction in enzymatic activity in the homozygous mutants compared to the parental strain.
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