An N-ethyl-N-nitrosourea-induced mutation in N-acetyltransferase 1 in mice

作者:Erickson Robert P*; McQueen Charlene A; Chau Binh; Gokhale Vijay; Uchiyama Masahi; Toyoda Atsushi; Ejima Fumiwo; Maho Naka; Sakaki Yoshiyuki; Gondo Yoichi
来源:Biochemical and Biophysical Research Communications, 2008, 370(2): 285-288.
DOI:10.1016/j.bbrc.2008.03.085

摘要

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.

  • 出版日期2008-5-30