The metallothionein-I gene maps to mouse chromosome 8: implications for human Menkes' disease

We have assigned the structural gene (Mt-1) coding for the murine metal-binding protein metallothionein I (MT-1) to mouse chromosome 8 by using a cloned DNA probe for mouse Mt-1 in combination with a panel of Chinese hamster-mouse somatic cell hybrid clones segregating mouse chromosomes. Analysis of hybrid cell extracts for the presence of mouse Mt-1 or MT-1 mRNA revealed concordant segregation of Mt-1 with mouse glutathione reductase, an enzyme marker for mouse chromosome 8, but discordant segregation with enzyme markers for 14 other mouse chromosomes. Karyotype analyses of seven informative hybrid clones confirmed the assignment of mouse Mt-1 to chromosome 8. Menkes' disease in man and the mottled mutation (Mo) in the mouse, which provides an animal model of Menkes' disease, are both X-linked degenerative neurologic disorders involving abnormal copper metabolism and increased levels of intracellular metallothionein protein. Fibroblasts from Mo male mice have increased amounts of MT-1 mRNA, suggesting that both Mo and Menkes' disease may be due to a metallothionein gene mutation. However, our assignment of Mt-1 to mouse chromosome 8, rather than the X chromosome, demonstrates that a mutation in mouse Mt-1 or a closely linked regulatory gene is not the primary defect in Mo, and implies that a metallothionein gene mutation is not the genetic defect in human Menkes' disease.