Cox D R, Palmiter R D
Hum Genet. 1983;64(1):61-4. doi: 10.1007/BF00289481.
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.
我们通过使用小鼠金属硫蛋白I（MT-1）的克隆DNA探针与一组分离小鼠染色体的中国仓鼠-小鼠体细胞杂交克隆相结合，将编码小鼠金属结合蛋白金属硫蛋白I（MT-1）的结构基因（Mt-1）定位到小鼠8号染色体上。对杂交细胞提取物中是否存在小鼠Mt-1或MT-1 mRNA的分析表明，Mt-1与小鼠谷胱甘肽还原酶（一种小鼠8号染色体的酶标记物）呈一致分离，但与其他14条小鼠染色体的酶标记物呈不一致分离。对七个信息丰富的杂交克隆进行核型分析，证实了小鼠Mt-1定位于8号染色体。人类的门克斯病和小鼠的斑驳突变（Mo）（它提供了门克斯病的动物模型）都是X连锁的退行性神经系统疾病，涉及异常的铜代谢和细胞内金属硫蛋白水平升高。来自Mo雄性小鼠的成纤维细胞中MT-1 mRNA含量增加，这表明Mo和门克斯病可能都是由于金属硫蛋白基因突变所致。然而，我们将Mt-1定位到小鼠8号染色体而非X染色体上，这表明小鼠Mt-1或紧密连锁的调控基因的突变不是Mo的主要缺陷，并且意味着金属硫蛋白基因突变不是人类门克斯病的遗传缺陷。
