REGIONAL DISTRIBUTION OF METALLOTHIONEIN AND ZINC IN THE MOUSE GUT - COMPARISON WITH METALLOTHIONIEN-NULL MICE

Gut Zn homeostatic responses to low, replete, and excess dietary Zn (1 0, 150, and 400 mg Zn/kg, respectively) were compared in mice with (MT +/+) and without (MT-/-) metallothionein (MT) expression. MT concentra tions decreased progressively from stomach (12.9 nmol Cd bound/g) to c olon (4.6 nmol Cd bound/g). Small intestinal MT was increased in mice fed the 400-mg Zn/kg diet (+130%, duodenum; +56%, jejunum; +29%, termi nal ileum), but not in the stomach, cecum and colon. Zn concentrations were much higher in the distal gut at increasing Zn intakes in MT+/mice but to a lesser extent in MT-/- mice. On the 10-mg Zn/kg diet, MT -/- mice had 45% more Zn in the jejunum/ileum than MT+/+ mice. In fast ed (20 h) mice, Zn concentrations in all gut regions were similar to t hose of MT+/+ mice fed the 10-mg Zn/kg diet, irrespective of prior Zn intake or genotype. Liver MT quadrupled in mice fasted after the 10-mg Zn/kg diet but only doubled after the 400-mg Zn/kg diet, a trend also present in gut MT. Glucagon administration stimulated gut as well as liver MT, implicating it as a major component of the MT response to fa sting. MT-/- mice had five times more variation than MT+/+ mice in pla sma Zn over all dietary groups. Together, these findings demonstrate t hat without MT, there is little modification of regional gut Zn concen trations in response to extremes of dietary Zn and poorer regulation o f Zn homeostasis.