Targeted disruption of metallothionein I and II genes increases sensitivity to cadmium.
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.
Masters
B A
BA
Laboratory of Reproductive Physiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia 19104.
Kelly
E J
EJ
Quaife
C J
CJ
Brinster
R L
RL
Palmiter
R D
RD
D000410:Alanine Transaminase / Q000097:blood; D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D001483:Base Sequence; D002105:Cadmium Poisoning / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D004247:DNA / Q000235:genetics; D005260:Female; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008297:Male; D008668:Metallothionein / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D008969:Molecular Sequence Data; D016254:Mutagenesis, Insertional; D014176:Protein Biosynthesis; D014158:Transcription, Genetic
D004247:DNA; D008668:Metallothionein; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase