Transgenic mice that overexpress metallothionein-I resist dietary zinc deficiency.
Transgenic mice that overexpress metallothionein-I (MT-I) accumulate mo re MT-I and zinc in major organs than do control mice. The effects of overexpression of MT-I on resistance to dietary zinc deficiency were examined by feeding transgenic and control mice a zinc-deficient (0.5-1.5 micron/gram) or a zinc adequate (50 micron/g) diet and by measuring effects on pregnancy. When pregnant mice were maintained under conditions of dietary zinc deficiency, the number of resorptions and teratogenic defects of fetuses was greatly reduced in transgenic compared with control mice. Differences between transgenic and controls were not apparent at d 8 of pregnancy (d 1 = vaginal plug) but were apparent by d 14. This result suggests that the larger maternal zinc pool in the transgenic females allows fetal development to progress normally for a longer period of time. However, neither transgenic nor control zinc-deficient mice could complete pregnancy. Pancreatic MT concentrations were the greatest in zinc adequate transgenic mice. Moreover, there was >10-fold more MT per gram wet weight in the pancreas of transgenic mice than in any other organ examined. Pancreatic MT concentrations were an exceptionally sensitive indicator of zinc deficiency. Pancreatic MT declined 99.8% and zinc declined to basal levels by d 14 of pregnancy when transgenic and control mice were fed a zinc-deficient diet, whereas MT concentrations in other organs decreased only modestly. We suggest that the larger pool of zinc MT in the transgenic mice provides a biologically important labile pool of zinc during periods of zinc deficiency.
Dalton
T
T
Department of Biochemistry and Molecular Biology, University of Kansas Medical Center, Kansas City 66160-7421, USA.
Fu
K
K
Palmiter
R D
RD
Andrews
G K
GK
D000818:Animals; D000013:Congenital Abnormalities / Q000209:etiology; D005260:Female; D005327:Fetal Resorption / Q000209:etiology; D015870:Gene Expression; D008099:Liver / Q000378:metabolism; D008297:Male; D008668:Metallothionein / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D010179:Pancreas / Q000378:metabolism; D011247:Pregnancy; D011248:Pregnancy Complications; D012333:RNA, Messenger / Q000378:metabolism; D015032:Zinc / Q000172:deficiency* / Q000378:metabolism
D012333:RNA, Messenger; D008668:Metallothionein; D015032:Zinc