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

Robert P. Erickson, Charlene A. McQueen, Binh Chau, Vijay Gokhale, Masahi Uchiyama, Atsushi Toyoda, Fumiwo Ejima, Naka Maho, Yoshiyuki Sakaki, Yoichi Gondo

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Pages (from-to)285-288
Number of pages4
JournalBiochemical and Biophysical Research Communications
Volume370
Issue number2
DOIs
StatePublished - May 30 2008

Fingerprint

Ethylnitrosourea
hydrazine
Mutagenesis
Mutation
Acetyltransferases
Isoleucine
Isoniazid
Substrates
Threonine
Carcinogens
Amines
Molecular Models
Substitution reactions
Base Pairing
Pharmaceutical Preparations
Liver
N-acetyltransferase 1
Therapeutics

Keywords

  • Catalytic triad
  • Isoniazid metabolism
  • N-Acetyltransferase
  • N-Ethyl-N-nitrosourea mutagenesis

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

An N-ethyl-N-nitrosourea-induced mutation in N-acetyltransferase 1 in mice. / Erickson, Robert P.; McQueen, Charlene A.; Chau, Binh; Gokhale, Vijay; Uchiyama, Masahi; Toyoda, Atsushi; Ejima, Fumiwo; Maho, Naka; Sakaki, Yoshiyuki; Gondo, Yoichi.

In: Biochemical and Biophysical Research Communications, Vol. 370, No. 2, 30.05.2008, p. 285-288.

Research output: Contribution to journalArticle

Erickson, RP, McQueen, CA, Chau, B, Gokhale, V, Uchiyama, M, Toyoda, A, Ejima, F, Maho, N, Sakaki, Y & Gondo, Y 2008, 'An N-ethyl-N-nitrosourea-induced mutation in N-acetyltransferase 1 in mice', Biochemical and Biophysical Research Communications, vol. 370, no. 2, pp. 285-288. https://doi.org/10.1016/j.bbrc.2008.03.085
Erickson, Robert P. ; McQueen, Charlene A. ; Chau, Binh ; Gokhale, Vijay ; Uchiyama, Masahi ; Toyoda, Atsushi ; Ejima, Fumiwo ; Maho, Naka ; Sakaki, Yoshiyuki ; Gondo, Yoichi. / An N-ethyl-N-nitrosourea-induced mutation in N-acetyltransferase 1 in mice. In: Biochemical and Biophysical Research Communications. 2008 ; Vol. 370, No. 2. pp. 285-288.
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