The mouse acrodermatitis enteropathica gene Slc39a4 (Zip4) is essential for early development and heterozygosity causes hypersensitivity to zinc deficiency.

Abstract	The human Zip4 gene (Slc39a4) is mutated in the rare recessive genetic disorder of zinc metabolism acrodermatitis enteropathica, but the physiological functions of Zip4 are not well understood. Herein we demonstrate that homozygous Zip4-knockout mouse embryos die during early morphogenesis and heterozygous offspring are significantly underrepresented. At mid-gestation, an array of developmental defects including exencephalia, anophthalmia and severe growth retardation were noted in heterozygous embryos, and at weaning, many (63/280) heterozygous offspring were hydrocephalic, growth retarded and missing one or both eyes. Maternal dietary zinc deficiency during pregnancy exacerbated these effects, whereas zinc excess ameliorated these effects and protected embryonic development of heterozygotes but failed to rescue homozygous embryos. Heterozygous Zip4 embryos were not underrepresented in litters from wild-type mothers, but were approximately 10 times more likely to develop abnormally than were their wild-type littermates during zinc deficiency. Thus, both embryonic and maternal Zip4 gene expressions are critical for proper zinc homeostasis. These studies suggest that heterozygous mutations in the acrodermatitis gene Zip4 may be associated with a wider range of developmental defects than was previously appreciated, particularly when dietary zinc is limiting.
Authors	Jodi Dufner-Beattie, Benjamin P Weaver, Jim Geiser, Mehmet Bilgen, Melissa Larson, Wenhao Xu, Glen K Andrews
Journal	Human molecular genetics (Hum Mol Genet) Vol. 16 Issue 12 Pg. 1391-9 (Jun 15 2007) ISSN: 0964-6906 [Print] England
PMID	17483098 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
Chemical References	Cation Transport Proteins Slc39a4 protein, mouse Zinc
Topics	Acrodermatitis (genetics) Alleles Animals Cation Transport Proteins (genetics, metabolism) Cells, Cultured Embryo, Mammalian (metabolism) Embryonic Development Endoderm (metabolism) Female Heterozygote Homozygote Male Mice Mice, Inbred C57BL Mice, Inbred Strains Mice, Knockout Microscopy, Fluorescence Models, Genetic Zinc (deficiency, metabolism)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.

Realize the full power of the drug-disease research graph!