Induction of metallothionein by zinc in lethal milk mutant mice

Adult lethal milk (lm/lm) mutant mice display increased induction of hepatic metallothionein synthesis compared to wild-type mice following the subcutaneous injection of 40 µmol ZnCl₂/kg mouse. At this zinc dose the rate of incorporation of |³⁵S| cysteine into hepatic metallothionein in adult (100-to 230-day-old) lm/lm mice was approximately 2.4-fold greater than the rate of incorporation of isotope in wild-type animals. At a higher zinc dose (160 µmol ZnCl₂/kg) the incorporation of |³⁵S| cysteine into hepatic metallothionein was similar in lm/lm and wild-type mice. The altered dose-response to zinc administration was not due to a change in hepatic zinc, copper, or manganese levels, to a difference in ⁶⁵Zn uptake, or to an alteration in ⁶⁵Zn bound to differential centrifugation fractions of adult lm/lm liver. ⁶⁵Zn bound to hepatic metallothionein was, however, increased in aging lm/lm mice with symptomatic skin lesions.