Roles of members of the ZnT family (SiC30A) in zinc absorption and homeostasis

Zinc is an essential trace element required by all living organisms. Changes in zinc absorption and excretion in the gastrointestinal tract are the primary mechanisms for maintaining zinc homeostasis, and intracellular zinc homeostasis is maintained through a coordinated regulation by different proteins involved in uptake, excretion and intracellular storage/trafficking of zinc. ZnT proteins are characterized by their ability to decrease the cytoplasmic zinc concentration by transporting zinc out of cells or into intracellular compartments. The first study undertook immunoreactivities of ZnT1, 4, 5 6 and 7 in the mouse gastrointestinal tract for comparison of the expression and cellular localization of these proteins. The results demonstrate a dominant epithelial cell distribution for all ZnT proteins examined along the mouse gastrointestinal tract with specific expression patterns, cell types, and localization for each ZnT protein. The abundant expression of ZnT proteins in the absorptive epithelial cell of the gastrointestinal tract suggests that ZnT proteins may play important roles in dietary zinc absorption and endogenous zinc secretion.; ZnT7 is highly expressed in the small intestine and immunohistochemical analysis showed that ZnT7 is localized along the gastrointestinal tract. To investigate the physiological function of ZnT7, a null mutant of Znt7 mouse line was generated by gene trapping technology. Znt7 null mutant mice are fertile and viable with no behavioral abnormalities. Serum zinc concentrations are in normal ranges in the null mutant mice. However, the ZnT7 null mutant mice show retarded growth despite normal food intake. Body composition analysis showed that the ZnT7 null mice had a significantly lower body fat mass than controls. Mutant mice also showed reduced 65Zn accumulation in small intestine, liver, spleen and kidney. Embryonic fibroblast cells isolated from the mutant embryos result in lower accumulation of 65Zn compare with the controls, supporting the previous study that ZnT7 play important roles in zinc homeostasis by storing intracellular zinc. Inactivation of ZnT7 may influence intracellular zinc homeostasis that might secondary affect cell metabolism or fat metabolism.