ZINC KINETICS IN METALLOTHIONEIN KNOCKOUT MICE

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This application proposes to study the impact of metallothionein-(MTI) and metallothionein-II (MTII) in MTI/MTII null or knockout mice on Zn kinetics. The aim is to use the PI's long-standing mineral modeling expertise using SAAM, and a previously developed model for Zn kinetics in wild-type rats to study the role of MTs in the regulation of Zn absorption and distribution. The hypothesis is that MT will have a role in homeostasis, although the site of this impact is not clearly identified in the proposal. Specifically, wild-type and null mice will be fed diets containing 35 or 100 mg Zn/kg diet, and half of the animals will receive 65Zn orally and half will receive 65Zn by i.v. injection. Zn kinetics will be followed over an eight day period. The specific aims of the study are: 1) to identify differences in Zn kinetics due to deletion of the two major MTs; 2) to use these differences to identify a role for MT in Zn homeostasis.