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  • Title: Transcriptional induction of metallothionein-I and -II genes in the livers of Cu,Zn-superoxide dismutase knockout mice.
    Author: Ghoshal K, Majumder S, Li Z, Bray TM, Jacob ST.
    Journal: Biochem Biophys Res Commun; 1999 Nov 02; 264(3):735-42. PubMed ID: 10544001.
    Abstract:
    The levels of metallothionein-I and -II (MT-I and MT-II) mRNAs were elevated (10- to 12-fold), specifically in the livers of mice with homozygous deletion of the gene for Cu,Zn-SOD (Sod1-/-), the enzyme that catalyzes the removal of O(-)(2). The induction of MT mRNA occurred primarily at the level of transcription. In vivo genomic footprinting of the MT-I promoter region revealed distinctive footprinting at MRE-d, MRE-c, and MLTF/ARE sites in the livers of knockout mice. MTF-1, the key factor responsible for the heavy-metal and oxidative stress-induced expression of the MT-I gene, was activated 3-fold in the nuclear extract from the livers of Cu,Zn-SOD null mice. Because metallothioneins are potent scavengers of reactive oxygen species and protect cells from oxidative stress, the apparent normal characteristics of the mice with the disrupted Cu, Zn-SOD gene are probably due to overexpression of MT-I and MT-II in the livers of these animals.
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