Targeting and germ-line transmission of a null mutation at the metallothionein I and II loci in mouse

Proc Natl Acad Sci U S A. 1993 Sep 1;90(17):8088-92. doi: 10.1073/pnas.90.17.8088.


We report the generation of transgenic mice deficient in the metallothionein MT-I and MT-II genes. The mutations were introduced into embryonic stem cells by homologous recombination. Chimeric mice resulting from the targeted embryonic stem cells transmitted the disrupted alleles through their germ line. Homozygous animals were born alive and appeared phenotypically normal and fertile. Absence of MT proteins was confirmed by direct measurement in liver extracts. Challenging the mutant animals with moderate levels of CdSO4 indicated their greater susceptibility to cadmium toxicity than wild-type animals. These mice should provide a useful model to allow detailed study of the physiological roles of MT-I and MT-II.

Publication types

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

MeSH terms

  • Animals
  • Base Sequence
  • Blotting, Southern
  • Chimera
  • Crosses, Genetic
  • DNA / genetics
  • DNA / isolation & purification
  • Embryo, Mammalian
  • Female
  • Genetic Carrier Screening
  • Homozygote
  • Male
  • Metallothionein / deficiency
  • Metallothionein / genetics*
  • Mice / genetics*
  • Mice, Inbred C57BL / genetics
  • Molecular Sequence Data
  • Mutation*
  • Oligodeoxyribonucleotides
  • Polymerase Chain Reaction / methods
  • Recombination, Genetic*
  • Restriction Mapping
  • Stem Cells / metabolism


  • Oligodeoxyribonucleotides
  • DNA
  • Metallothionein