TARGETED DISRUPTION OF METALLOTHIONEIN-I AND METALLOTHIONEIN-II GENESINCREASES SENSITIVITY TO CADMIUM

We inactivated the mouse metallothionein (MT)-I and MT-II genes in emb ryonic stem cells and generated mice homozygous for these mutant allel es. These mice were viable and reproduced normally when reared under n ormal laboratory conditions. They were, however, more susceptible to h epatic poisoning by cadmium. This proves that these widely expressed M Ts are not essential for development but that they do protect against cadmium toxicity. These mice provide a means for testing other propose d functions of MT in vivo.