The Znt4 mutation inlethal milk mice affects intestinal zinc homeostasis through the expression of other Zn transporters

Murgia, Chiara; Vespignani, Isabella; Rami, Rita; Perozzi, Giuditta

doi:10.1007/bf02829937

Cited by 18 publications

(11 citation statements)

References 45 publications

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“…The absence of the zinc secretion activity mediated by zinc transporters results in increased intracellular zinc concentration. Other zinc efflux activities are able to maintain the level of zinc ions below the threshold necessary for full induction of metallothioneins (Murgia and others ). The potential role of zinc in poultry immune response, Salmonella infection, and molting was studied (Park and others ).…”

Section: Role Of Zinc In Pregnancymentioning

confidence: 99%

Zinc: The Metal of Life

Kaur

Gupta

Saraf

et al. 2014

Comp Rev Food Sci Food Safe

161

103

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The importance of zinc was 1st reported for Aspergillus niger. It took over 75 y to realize that zinc is also an essential trace element for rats, and an additional 30 y went by before it was recognized that this was also true for humans. The adult body contains about 2 to 3 g of zinc. Zinc is found in organs, tissues, bones, fluids, and cells. It is essential for many physiological functions and plays a significant role in a number of enzyme actions in the living systems. Bioinformatics estimates report that 10% of the human proteome contains zinc-binding sites. Based on its role in such a plethora of cellular components, zinc has diverse biological functions from enzymatic catalysis to playing a crucial role in cellular neuronal systems. Thus, based on the various published studies and reports, it is pertinent to state that zinc is one of the most important essential trace metals in human nutrition and lifestyle. Its deficiency may severely affect the homeostasis of a biological system. This review compiles the role of zinc in prophylaxis/therapeutics and provides current information about its effect on living beings.

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Section: Role Of Zinc In Pregnancymentioning

confidence: 99%

Zinc: The Metal of Life

Kaur

Gupta

Saraf

et al. 2014

Comp Rev Food Sci Food Safe

161

103

View full text Add to dashboard Cite

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“…First, lm mice suckled on wild type dams exhibited normal zinc homeostasis until 8 months of age, when they began to exhibit signs of zinc deficiency including alopecia, dermatitis, and premature sterility (58,59). Second, ZnT4 expression in rodent small intestine was restricted to epithelium of the villus compared to the crypts (14,57), and the immunolocalization of ZnT4 in enterocytes was primarily basolateral in growing rats (57).…”

Section: Zinc Transporters In Vesiclesmentioning

confidence: 99%

Dietary zinc absorption: A play of Zips and ZnTs in the gut

2010

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SummaryStudies on dietary zinc absorption are of fundamental nutritional significance, owing to the ubiquity of zinc in biological processes and the severe outcomes of zinc deficiency in humans. Insights into the molecular basis of dietary zinc absorption have advanced in recent years through functional characterization of zinc transporters in cell culture, immunohistochemical studies on rodent intestine and analysis of gene knockout mice. Zinc transporters with manifested expression in enterocytes include ZnT1, ZnT2, ZnT4, ZnT5, ZnT6, ZnT7, Zip4, and Zip5. Among them, ZIP4, the gene responsible for Acrodermatitis enteropathica, an inherited human zinc deficiency, mediates dietary zinc uptake into enterocytes across the apical membrane, while ZnT1 is involved in zinc efflux from enterocytes across the basolateral membrane into circulation. The intracellular trafficking pathways for zinc retention and movement between apical and basolateral sides of the enterocytes have yet to be defined. The utilization of Drosophila model in elucidating molecular mechanisms of dietary zinc absorption is also discussed in this review.

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“…The lethal milk (lm) mutant mice carry a loss of function mutation in the ZnT4 gene which results in reduced zinc secretion into the milk produced in epithelial mammary gland cells (Dufner-Beattie et al, 2006). As a result, homozygous lm/lm pups suckling from lm/lm dams do not survive past the first 2weeks of neonatal development (Murgia et al, 2006). Mice with impaired ZIP1, ZIP2 or ZIP3 function display a decreased ability to absorb zinc from the diet, particularly during pregnancy when zinc absorption is normally increased (Dufner-Beattie et al, 2005;Dufner-Beattie et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

Systematic functional characterization of putative zinc transport genes and identification of zinc toxicosis phenotypes inDrosophila melanogaster

Lye

Richards

Dechen

et al. 2012

Journal of Experimental Biology

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SUMMARYThe heavy metal zinc is an essential component of the human diet and is incorporated as a structural component in up to 10% of all mammalian proteins. The physiological importance of zinc homeostasis at the cellular level and the molecular mechanisms involved in this process have become topics of increasing interest in recent years. We have performed a systematic functional characterization of the majority of the predicted Drosophila Zip (zinc/iron regulated transporter-related protein) and ZnT genes, using the Gal4-UAS system to carry out both ubiquitous and targeted over-expression and suppression studies for 13 of the 17 putative zinc transport genes identified to date. We found that six of these 13 genes may be essential for fly viability and that three of the remaining seven demonstrate over-expression phenotypes. Our findings reaffirm the previously proposed function of dZnT63C (CG17723: FBgn005432) as an important zinc efflux protein and indicate that the fly homolog of hZip1, dZip42C.1 (CG9428: FBgn0033096), is a strong zinc importer in Drosophila. By combining over-expression of dZip42C.1 with suppression of dZnT63C we were able to produce easily identifiable zinc toxicosis phenotypes, which can be rescued or worsened by modifying dietary zinc content. Our findings show that a genetically based zinc toxicosis situation can be therapeutically treated or exacerbated by modifications to the diet, providing a sensitized background for future, more detailed studies of Zip/ZnT function. Supplementary material available online at

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The Znt4 mutation inlethal milk mice affects intestinal zinc homeostasis through the expression of other Zn transporters

Cited by 18 publications

References 45 publications

Zinc: The Metal of Life

Zinc: The Metal of Life

Dietary zinc absorption: A play of Zips and ZnTs in the gut

Systematic functional characterization of putative zinc transport genes and identification of zinc toxicosis phenotypes inDrosophila melanogaster

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