Mouse ZIP1 and ZIP3 genes together are essential for adaptation to dietary zinc deficiency during pregnancy

Abstract

Subfamily II of the solute-linked carrier 39A superfamily contains three well-conserved zinc transporters (ZIPs1, 2, 3) whose physiological functions are unknown. We generated mice homozygous for knockout alleles of ZIP1 and both ZIP1 and ZIP 3 (double-knockout). These mice were apparently normal when dietary zinc was replete, but when dietary zinc was limited during pregnancy embryos from ZIP1 or ZIP3 knockout mice were two to three times more likely to develop abnormally than those in wildtype mice, and 91% (71/78) of embryos developed abnormally in ZIP1, ZIP3 double-knockout mice. Analysis of the patterns of expression of these genes in mice revealed predominate expression in intestinal stromal cells, nephric-tubular epithelial cells, pancreatic ductal epithelial cells, and hepatocytes surrounding the central vein. This suggests that these zinc transporters function, at least in part, in the redistribution and/or retention of zinc rather than its acquisition from the diet. In conclusion, mutations in the ZIP1 and ZIP3 zinc transporter genes are silent when dietary intake of zinc is normal, but can dramatically compromise the success of pregnancy when dietary intake of zinc is limiting.

Novel antigens in type 1 diabetes: The importance of ZnT8

“…Others such as ZnT3 -/- [24] show remarkably weak phenotypes in spite of specifi c tissue and subcellular distribution. Mice with a triple knockout of Zip1, -2, and -3 have no phenotype [25] except under conditions of dietary Zn defi ciency [26].…”

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

“…In vivo studies have produced a large amount of data regarding zinc transporter function (Falcón-Pérez, Dell'Angelica, 2007;Mao et al, 2007;Murakami and Hirano, 2008;Ohana et al, 2009). 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).…”

“…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). The ZnT8 knockout (KO) mouse model, which displays decreased insulin secretion, has provided insights into the endogenous function of ZnT8 as an importer of zinc into insulin-containing granules in pancreatic -cell islets (Hardy et al, 2011).…”

Catalase and Carbonic Anhydrase Enzyme Activities, and Some Mineral-Heavy Metal Concentrations in Newborns with Congenital Malformations

“…It is al so in te res ting to no te that zinc de fi ci ency in hu mans Turkiye Klinikleri J Med Sci 2011;31 (2) has be en cor re la ted with ab nor mal fe tal de ve lopment, di a be tes and schi zop hre ni a, dec re a sed cog niti ve be ha vi or and in tel lec tu al de ve lop ment, and in cre a sed mor ta lity and di se a se. 44 Dec re a sed gas troin tes ti nal ab sorp ti on and tis su e-spe ci fic ab sorp ti on of Zn may ha ve con tri bu tory ef fects. The le vels of Zn we re dec re a sed in the sera of new borns with con ge ni tal malformations when com pa red to the con trol gro up (Tab le 2).…”