Expression of the mouse metallothionein-I and -II genes provides a reproductive advantage during maternal dietary zinc deficiency.
The function of metallothionein in zinc homeostasis was examined by using mice homozygous for knockout (KO) of the metallothionein-I or -II (MT-I and MT-II) genes. Pregnant MT-I/II KO mice or control mice were fed a zinc-deficient (1 microg/g or 5 microg/g) diet or a zinc-adequate (50 microg/g) diet during specific periods of pregnancy, and the effects on morphogenesis of the embryos were determined at day 14 of pregnancy (day 1 = vaginal plug). In the homozygous MT-I/II KO, as well as in the nontransgenic control mice, severe dietary zinc deficiency (1 microg/g) beginning on day 1 of pregnancy was embryotoxic and teratogenic, and the majority of the embryos in both strains were dead by mid-gestation. However, 53% of the surviving embryos in the MT-I/II KO mice were morphologically abnormal compared to only 32% of the embryos in the control mice. In subsequent experiments, moderate dietary zinc deficiency (5 microg/g beginning on day 1 of pregnancy or 1 microg/g dietary zinc beginning on day 8 of pregnancy) exerted teratogenic, but not embryotoxic effects. Embryos in the MT-I/II KO mice were 260 to 290% as likely to develop abnormally than were embryos in the control mice fed these same diets. These results demonstrate that the expression of the MT-I and -II genes in pregnant females improves reproductive success during maternal dietary zinc deficiency.
Andrews
G K
GK
Department of Biochemistry and Molecular Biology, University of Kansas Medical Center, Kansas City, KS 66160-7421, USA.
Geiser
J
J
D000818:Animals; D002104:Cadmium / Q000378:metabolism; D004032:Diet; D004622:Embryo, Mammalian / Q000002:abnormalities / Q000378:metabolism; D005260:Female; D005333:Fetus / Q000002:abnormalities / Q000378:metabolism; D005786:Gene Expression Regulation; D005838:Genotype; D006706:Homeostasis / Q000235:genetics; D006720:Homozygote; D008668:Metallothionein / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D011247:Pregnancy; D018873:Pregnancy Rate; D015032:Zinc / Q000008:administration & dosage / Q000172:deficiency*
D002104:Cadmium; D008668:Metallothionein; D015032:Zinc