Slc39a1 to 3 (subfamily II) Zip genes in mice have unique cell-specific functions during adaptation to zinc deficiency

Taiho Kambe, Jim Geiser, Brett Lahner, David E. Salt, Glen K. Andrews

Research output: Contribution to journalArticlepeer-review

49 Citations (Scopus)


Slc39a1 to 3 ( subfamily II) Zip genes in mice have unique cell-specific functions during adaptation to zinc deficiency. Am J Physiol Regul Integr Comp Physiol 294: R1474-R1481, 2008. First published March 19, 2008; doi:10.1152/ajpregu.00130.2008.-Subfamily II of the solute carrier ( Slc) 39a family contains three highly conserved members ( ZIPs 1-3) that share a 12-amino acid signature sequence present in the putative fourth transmembrane domain and function as zinc transporters in transfected cells. The physiological significance of this genetic redundancy is unknown. Here we report that the complete elimination of all three of these Zip genes, by targeted mutagenesis and crossbreeding mice, causes no overt phenotypic effect. When mice were fed a zinc-adequate diet, several indicators of zinc status were indistinguishable between wild-type and triple-knockout mice, including embryonic morphogenesis and growth, alkaline phosphatase activity in the embryo, ZIP4 protein in the visceral yolk sac, and initial rates ( 30 min) of accumulation/retention of Zn-67 in liver and pancreas. When mice were fed a zinc-deficient diet, embryonic membrane-bound alkaline phosphatase activity was reduced to a much greater extent, and 80% of the embryos of the triple-knockout mice developed abnormally compared with 12% of the embryos of wildtype mice. During zinc deficiency, the accumulation/retention ( 3 h) of 67Zn in the liver and pancreas of weanlings was significantly impaired in the triple-knockout mice compared with wild-type mice. Thus none of these three mammalian Zip genes apparently plays a critical role in zinc homeostasis when zinc is replete, but they play important, noncompensatory roles when this metal is deficient.

Original languageEnglish
Pages (from-to)R1474-R1481
Number of pages8
JournalAmerican Journal of Physiology-Regulatory Integrative and Comparative Physiology
Issue number5
Publication statusPublished - 1 May 2008


  • pregnancy
  • stable zinc isotope
  • triple-knockout mice
  • zinc homeostasis
  • acrodermatitis-enteropathica
  • uptake transporter
  • LIV-1 subfamily
  • alkaline-phosphatases
  • dietary zinc
  • mouse ZIP1
  • family
  • expression
  • proteins
  • lacking


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