TARGETING AND GERM-LINE TRANSMISSION OF A NULL MUTATION AT THE METALLOTHIONEIN I-LOCI AND II-LOCI IN MOUSE

We report the generation of transgenic mice deficient in the metalloth ionein MT-I and MT-II genes. The mutations were introduced into embryo nic stem cells by homologous recombination. Chimeric mice resulting fr om the targeted embryonic stem cells transmitted the disrupted alleles through their germ line. Homozygous animals were born alive and appea red phenotypically normal and fertile. Absence of MT proteins was conf irmed by direct measurement in liver extracts. Challenging the mutant animals with moderate levels of CdSO4 indicated their greater suscepti bility to cadmium toxicity than wild-type animals. These mice should p rovide a useful model to allow detailed study of the physiological rol es of MT-I and MT-II.