Pancreatic metallothionein-I may play a role in zinc homeostasis during maternal dietary zinc deficiency in mice.
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.
Lee
Dae Kee
DK
Department of Biochemistry and Molecular Biology, University of Kansas Medical Center, Kansas City 66160-7421, USA.
Geiser
Jim
J
Dufner-Beattie
Jodi
J
Andrews
Glen K
GK
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*
D020799:Pancrelipase; D008668:Metallothionein; D015032:Zinc