The SLC39A (solute carrier 39A) [ZIP (Zrt-Irt-like protein)] family consists of 14 members which are thought to control zinc uptake into the cytoplasm. Among these, ZIP4 is known to be particularly important for zinc homoeostasis. Mutations in this gene cause acrodermatitis enteropathica, a rare recessive-lethal human genetic disorder. In the present paper, our studies of the regulation and function of the mouse Zip4 gene are briefly reviewed. Mouse Zip4 is expressed at highest levels in tissues involved in absorption of dietary or maternal zinc, and the gene and protein are dynamically regulated by multiple post-transcriptional mechanisms in response to zinc availability. ZIP4 accumulates at the apical surface of enterocytes and endoderm cells when zinc is deficient, because of increased stability of the mRNA and stabilization of the protein. In contrast, when zinc is replenished, the mRNA is destabilized and the protein is internalized and degraded rapidly. The critical importance of ZIP4 in zinc homoeostasis is revealed in mice with targeted deletions of this gene. Homozygous Zip4-knockout embryos die during early morphogenesis and heterozygous offspring are significantly underrepresented and display an array of developmental defects, including exencephalia, anophthalmia and severe growth retardation. Mice heterozygous for Zip4-knockout are hypersensitive to zinc deficiency, which suggests that humans heterozygous for this gene may also be very sensitive to zinc deficiency.
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Conference Article|
November 19 2008
Regulation and function of Zip4, the acrodermatitis enteropathica gene
Glen K. Andrews
1Department of Biochemistry and Molecular Biology, University of Kansas Medical Center, Kansas City, KS 66160-7421, U.S.A.
2email gandrews@kumc.edu
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Publisher: Portland Press Ltd
Received:
May 19 2008
Online ISSN: 1470-8752
Print ISSN: 0300-5127
© The Authors Journal compilation © 2008 Biochemical Society
2008
Biochem Soc Trans (2008) 36 (6): 1242–1246.
Article history
Received:
May 19 2008
Citation
Glen K. Andrews; Regulation and function of Zip4, the acrodermatitis enteropathica gene. Biochem Soc Trans 1 December 2008; 36 (6): 1242–1246. doi: https://doi.org/10.1042/BST0361242
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