THE MOTTLED GENE IS THE MOUSE HOMOLOG OF THE MENKES DISEASE GENE

The mottled mouse has been proposed as an animal model for Menkes dise ase, an X- linked disorder of copper transport. The recent isolation o f a copper-transporting ATPase gene responsible for Menkes disease has allowed us to test this hypothesis. Here we report the isolation and sequence of the mouse homologue of this gene. We show that two mottled (Mo) alleles, dappled (Mo-dp) and blotchy (Mo-blo), have abnormalitie s in the murine mRNA and that Mo-dp has a partial gene deletion. These studies prove that the mottled mouse is the murine model for Menkes d isease, providing the basis for future biochemical and therapeutic stu dies.