Metallothionein gene regulation in Menkes' syndrome.

The characteristic feature of Menkes' disease is a maldistribution of bodily copper; decreased copper levels are present in the serum, brain, and liver, whereas excess levels are present in gut, kidney, and most other nonhepatic tissues. Using cultured fibroblasts, we have shown that low extracellular copper concentrations induce synthesis of metallothionein, a copper-binding protein, in Menkes' cells but not in normal cells. This is due to a defect in a diffusable regulatory factor that is probably involved in copper metabolism. To further understand the role of the defective factor in transcription, assays have been developed to study the metal-dependent binding of nuclear proteins to metallothionein gene control sequences.