Metallothioneins (MTs) are low-molecular-mass cysteine-rich proteins implicated in metal homoeostasis and resistance to toxicity induced by heavy metals and alkylating agents. We report high hepatic MT protein accumulation (greater than 100-fold compared with wild-type mice) in toxic milk (tx) mice, along with markedly higher cytosol copper and zinc levels. Increased MT-gene transcription alone could not account for the high constitutive MT protein levels, since MT mRNA levels were not increased in tx mouse livers. However, hepatic MT was significantly more stable in adult tx mice: MT half-life (t1/2) was 79 or 77% greater than in wild-type mice before and after Cd induction respectively. Cd or Zn treatment increased MT mRNA, but not MT protein, accumulation in tx mouse livers: Cd displaced MT-bound Zn and Cu in preexisting MT. Thus tx mice appear to accumulate hepatic MT as a result of decreased protein degradation. These animals may provide a useful model to study the physiological role of MT, and human diseases (such as Wilson's disease) with abnormal copper metabolism.
Research Article| December 01 1993
A mutant mouse (tx) with increased hepatic metallothionein stability and accumulation
*Departments of Oncology, and Microbiology and Immunology, University of Western Ontario, 790 Commissioners Road East, London, Ontario, Canada N6A 4L6
†Department of Pathology, Health Sciences Centre, University of Western Ontario, London, Ontario, Canada N6A 5C1
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Biochem J (1993) 296 (2): 443–449.
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J Koropatnick, M G Cherian; A mutant mouse (tx) with increased hepatic metallothionein stability and accumulation. Biochem J 1 December 1993; 296 (2): 443–449. doi: https://doi.org/10.1042/bj2960443
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