title: Pancreatic metallothionein-I may play a role in zinc homeostasis during maternal dietary zinc deficiency in mice.
abstract: Herein, the function of pancreatic metallothionein (MT)-I during zinc deficiency in pregnancy was examined using transgenic mice, which constitutively express the mouse MT-I gene driven by the rat elastase I promoter. Pancreatic MT protein levels and zinc levels were elevated significantly in the transgenic mice compared with those in control mice. Pregnant transgenic and control mice were fed zinc-deficient (1 micro g/g beginning at d 8) or zinc-adequate (50 micro g/g) diets during pregnancy, and the effects on the morphology of embryos were determined at d 14 of pregnancy (d 1 = vaginal plug). As other indicators of zinc deficiency, maternal pancreatic MT levels, as well as the expression of zinc-regulated genes in the embryonic visceral yolk sac were examined. Under these experimental conditions of moderate dietary zinc deficiency, 21.3% of the embryos in control mice exhibited morphological defects, whereas only 5.8% of the embryos in the elastase-MT-I transgenic females had developed abnormally by d 14. Surprisingly, dietary zinc deficiency caused a >95% decrease in pancreatic MT protein concentration in these transgenic mice. This suggests the post-transcriptional control of MT protein levels during zinc deficiency because the rat elastase I promoter is not metal-regulated. The decrease in pancreatic MT protein levels was paralleled by a dramatic decrease in the relative abundance of MT-I mRNA and a dramatic increase in the relative abundance of the zinc/iron regulated transporter-related zinc transporter-4 (ZIP4) mRNA in the embryonic visceral yolk sac. Thus, the constitutive overexpression of pancreatic MT-I in these mice attenuated, but did not prevent the effects of maternal or embryonic zinc deficiency under these conditions. Overall, these findings are consistent with the hypothesis that mouse pancreatic MT-I may participate in providing a labile pool of maternal zinc for the developing embryo during periods of zinc deficiency.
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Kansas Medical Center, Kansas City 66160-7421, USA.
authors.forename: Dae Kee
authors.initials: DK
authors.lastname: Lee
authors.forename: Jim
authors.initials: J
authors.lastname: Geiser
authors.forename: Jodi
authors.initials: J
authors.lastname: Dufner-Beattie
authors.forename: Glen K
authors.initials: GK
authors.lastname: Andrews
mesh_terms: D000818:Animals; D004032:Diet; D005260:Female; D005838:Genotype; D006706:Homeostasis; D008668:Metallothionein / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D020799:Pancrelipase / Q000378:metabolism / Q000502:physiology*; D011247:Pregnancy; D015032:Zinc / Q000008:administration & dosage / Q000172:deficiency*
chemical_list: D020799:Pancrelipase; D008668:Metallothionein; D015032:Zinc