COPPER-METABOLISM IN METALLOTHIONEIN NULL MICE FED A HIGH-ZINC DIET

Humans and animals develop low copper (Cu) status when fed diets conta ining large amounts of zinc (Zn) far an extended period Current theory states that Zn-induced metallothionein (MT) in the intestinal mucosa binds Co and pi-events its absorption. We tested this theory by using a mouse model with a disruption in the MT gene that renders it incapab le of producing functional MT-I and MT-II (MT-null). If the theory is true, their the MT-null mouse should not develop low Cu status when fe d a high Zn diet. For I week, groups of 4-week-old MT-null and control mice were fed a diet that contained 35 mg Zn and < I mg Cu/kg. Each g enotype it ns then divided into two groups each. One group was fed a d iet containing 35 mg Zn and 1.5 mg Cu/kg and the other was fed a diet containing 400 mg Zn and 1.5 mg Cu/kg. After 14 days, plasma was harve sted and plasma ceruloplasmin amine oxidase (CPAO) activity, a good in dicator of Ctl status, was determined The plasma CPAO activity of cont rol mice fed 400 mg Zn/kg diet was 50% of that bz similar mice fed 35 mg Zn/kg. Likewise, plasma CPAO activity; in MT-null mice fed 400 mg Z n/kg diet was 40% of that in MT-null mice fed 35 mg Zn/kg. These data suggest that MT induction is nor required for the development of low C te status in mice fed a high Zn dirt and that the actual mechanism may involve the modulation or inhibition of a Cu transporter protein by Z n.