The Combined Inactivation of Intestinal and Hepatic ZIP14 Exacerbates Manganese Overload in Mice.

ZIP14 is a newly identified manganese transporter with high levels of expression in the small intestine and the liver. Loss-of-function mutations in can lead to systemic manganese overload, which primarily affects the central nervous system, causing neurological disorders. To elucidate the roles of intestinal ZIP14 and hepatic ZIP14 in maintaining systemic manganese homeostasis, we generated mice with single-tissue or two-tissue knockout, including intestine-specific (-In-KO), liver-specific (-L-KO), and double (intestine and liver) -knockout (-DKO) mice.