MUTATIONS IN THE MURINE HOMOLOG OF THE MENKES GENE IN DAPPLED AND BLOTCHY MICE

The murine homologue of the Menkes disease gene (MNK) was isolated fro m cDNA libraries, using human cDNA clones as probes, and by PCR. The p redicted amino acid sequence shows a high level of identity (89.9%) wi th the human protein, and the predicted functional domains in the huma n protein are present. Using probes to the mouse Mnk gene, we found th at the mottled dappled mutation was caused by alteration in the Mnk lo cus and lack of expression of Mnk RNA. Tissues of the blotchy mouse co ntained two larger sizes of MNK mRNA demonstrating a likely defect in RNA splicing. Thus, the mottled locus is homologous to the human MNK l ocus and dappled and blotchy are allelic mutations in this gene.