SIMILAR SPLICING MUTATIONS OF THE MENKES MOTTLED COPPER-TRANSPORTING ATPASE GENE IN OCCIPITAL HORN SYNDROME AND THE BLOTCHY MOUSE

The connective-tissue disorder occipital horn syndrome (OHS) is hypoth esized to be allelic to Menkes disease. The two diseases have differen t clinical presentations but have a similar abnormality of copper tran sport. Mice hemizygous for the blotchy allele of the X-linked mottled locus have similar connective-tissue defects as OHS and may represent a mouse model of this disease. We have analyzed the Menkes/mottled cop per-transporting ATPase in these two potentially homologous disorders and have identified similar splicing mutations in both. Some expressio n of normal mRNA was detectable by reverse transcription-PCR in the mu tant tissues. These findings contrast with the more debilitating mutat ions observed in Menkes disease and suggest that low amounts of an oth erwise normal protein product could result in the relatively mild phen otype of OHS and of the blotchy mouse.