Targeted disruption of metallothionein I and II genes increases sensitivity to cadmium

Proc Natl Acad Sci U S A. 1994 Jan 18;91(2):584-8. doi: 10.1073/pnas.91.2.584.


We inactivated the mouse metallothionein (MT)-I and MT-II genes in embryonic stem cells and generated mice homozygous for these mutant alleles. These mice were viable and reproduced normally when reared under normal laboratory conditions. They were, however, more susceptible to hepatic poisoning by cadmium. This proves that these widely expressed MTs are not essential for development but that they do protect against cadmium toxicity. These mice provide a means for testing other proposed functions of MT in vivo.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alanine Transaminase / blood
  • Alleles
  • Amino Acid Sequence
  • Animals
  • Aspartate Aminotransferases / blood
  • Base Sequence
  • Cadmium Poisoning / genetics*
  • Cadmium Poisoning / metabolism
  • Cadmium Poisoning / pathology
  • DNA / genetics
  • Female
  • Liver / drug effects
  • Liver / pathology
  • Male
  • Metallothionein / genetics*
  • Metallothionein / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Mutant Strains
  • Molecular Sequence Data
  • Mutagenesis, Insertional
  • Protein Biosynthesis
  • Transcription, Genetic


  • DNA
  • Metallothionein
  • Aspartate Aminotransferases
  • Alanine Transaminase