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Pure Appl. Chem., 2000, Vol. 72, No. 6, pp. 1023-1026

Use of genetically altered animal models in understanding the role of metallothionein in cadmium toxicity

Curtis D. Klaassen* and Supratim Choudhuri

Department of Pharmacology, Toxicology, and Therapeutics, University of Kansas Medical Center, Kansas City, KS 66160-7417, USA

Abstract: Acute Cd exposure produces liver injury, whereas chronic Cd exposure damages the kidney but not the liver. Previous experiments suggest that the low-molecular-weight, metal-binding protein metallothionein (MT) in liver protects against liver injury, but is responsible for the kidney injury observed after chronic Cd exposure. Thus, prior to the development of MT-transgenic and MT-knockout mice models, MT's role was always assumed to be a toxicological paradox, hepatoprotection but nephrotoxicity. The development of MT-transgenic and MT-knockout mice models has reconfirmed MT's protective role against Cd-induced hepatotoxicity, but it has challenged MT's suggested role in Cd-induced nephrotoxicity. In this communication, recent data using these genetically altered mice models indicate that MT protects against not only the Cd-induced hepatotoxicity, but also nephrotoxicity, hematotoxicity, immunotoxicity, and bone damage.