A NOVEL GENE INVOLVED IN ZINC TRANSPORT IS DEFICIENT IN THE LETHAL MILK MOUSE

We have identified the gene responsible for the inherited zinc deficie ncy in the lethal milk (lm) mouse. The gene, here designated Znt4, enc odes a 430-amino-acid protein that is homologous to two proteins, ZnT2 and ZnT3, responsible for sequestration of zinc into endosomal/lysoso mal compartments and synaptic vesicles, respectively. We show that the Znt4 gene confers zinc resistance to a zinc-sensitive yeast strain an d that it is abundantly expressed in the mammary epithelia and brain. The lethal milk mutant: has a nonsense mutation at arginine codon 297 in the Znt4 gene.