Intestinal metallothionein in lethal-milk mice with systemic zinc deficiency

Lethal-milk (C57BL/6J-lm) mice over 12 months of age exhibit clinical signs of systemic Zn deficiency. Such lm mice have increased concentrations of metallothionein (MT) in the intestinal mucosa. Various concentrations of Cd or Zn were added to the drinking water. MT was assayed using the Cd-saturation/hemolysate method and for sulfhydryl concentration (MT has 33% cysteine residues) with Ellman's reagent. As assayed by both methods, mucosa from untreated lm mice contained approximately twice as much MT as did the C57BL/6J-(+lm/+lm) (B6) controls. Treatment with 150 and 500 ppm Zn removed the genotypic differences observed for the untreated and Cd-treated mice. These results are consistent with the lm mutation affecting Zn metabolism through impaired MT metabolism as measured for the intestinal mucosa. These studies do not eliminate the possibility that the liver may also contribute.