title: An N-ethyl-N-nitrosourea-induced mutation in N-acetyltransferase 1 in mice.
abstract: 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.
authors: Department of Pediatrics, University of Arizona, 1501 N. Campbell Avenue, P.O. Box 245073, Tucson, AZ 85724, USA. erickson@peds.arizona.edu
authors: Robert P
authors: RP
authors: Erickson
authors: Charlene A
authors: CA
authors: McQueen
authors: Binh
authors: B
authors: Chau
authors: Vijay
authors: V
authors: Gokhale
authors: Masahi
authors: M
authors: Uchiyama
authors: Atsushi
authors: A
authors: Toyoda
authors: Fumiwo
authors: F
authors: Ejima
authors: Naka
authors: N
authors: Maho
authors: Yoshiyuki
authors: Y
authors: Sakaki
authors: Yoichi
authors: Y
authors: Gondo
mesh_terms: D000477:Alkylating Agents / Q000494:pharmacology*; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000818:Animals; D001191:Arylamine N-Acetyltransferase / Q000032:analysis / Q000235:genetics*; D002415:Cats; D006224:Cricetinae; D005038:Ethylnitrosourea / Q000494:pharmacology*; D014644:Genetic Variation; D006801:Humans; D007527:Isoenzymes / Q000032:analysis / Q000235:genetics*; D008099:Liver / Q000201:enzymology; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D016296:Mutagenesis; D009154:Mutation; D011817:Rabbits; D051381:Rats; D013379:Substrate Specificity / Q000235:genetics
chemical_list: D000477:Alkylating Agents; D007527:Isoenzymes; D001191:Arylamine N-Acetyltransferase; C089384:N-acetyltransferase 1; D005038:Ethylnitrosourea