Document Detail

Metallothionein knockout and transgenic mice exhibit altered intestinal processing of zinc with uniform zinc-dependent zinc transporter-1 expression.
MedLine Citation:
PMID:  9566988     Owner:  NLM     Status:  MEDLINE    
A role for metallothionein in intestinal zinc absorption has been the subject of considerable debate. If metallothionein affects zinc absorption, then those factors that induce metallothionein synthesis (e.g., heavy metals, hormones) should alter zinc absorption and homeostasis. The present studies used metallothionein transgenic mice (overexpressing) and metallothionein knockout mice (no expression of metallothionein-1 or metallothionein-2) to examine directly the effects of metallothionein on zinc absorption, independent of secondary effects that could be caused by metallothionein inducers. Zinc absorption was examined by administering a single oral zinc dose (0.5 mmol/kg) by feeding tube to metallothionein transgenic and metallothionein knockout mice and measuring the serum zinc concentration. Two hours after the dose, the serum zinc concentration was 2.3 times higher in metallothionein knockout mice than in their control strain. Conversely, the concentration was elevated only one third as much in the metallothionein transgenic mice as in their controls after the zinc dose. We found that the serum zinc concentration was inversely related to the level of metallothionein protein. The intestinal zinc content was higher in the metallothionein knockout mice, however, suggesting that metallothionein did not reduce zinc absorption by simply sequestering zinc in the mucosa. The expression of the zinc transporter ZnT-1 was directly related to the serum zinc level and was independent of the level of metallothionein. These results further support metallothionein as an important component for reducing the efficiency of zinc absorption at elevated zinc intakes.
S R Davis; R J McMahon; R J Cousins
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  The Journal of nutrition     Volume:  128     ISSN:  0022-3166     ISO Abbreviation:  J. Nutr.     Publication Date:  1998 May 
Date Detail:
Created Date:  1998-06-08     Completed Date:  1998-06-08     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0404243     Medline TA:  J Nutr     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  825-31     Citation Subset:  IM    
Food Science and Human Nutrition Department and Center for Nutritional Sciences, University of Florida, Gainesville, FL 32611, USA.
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MeSH Terms
Base Sequence
Cation Transport Proteins*
Cohort Studies
DNA Primers / chemistry
Gene Expression Regulation / genetics*
Intestinal Absorption / physiology*
Intestines / chemistry
Liver / chemistry
Membrane Proteins / biosynthesis,  genetics*
Metallothionein / analysis,  genetics,  physiology*
Mice, Inbred C57BL
Mice, Knockout
Mice, Transgenic
Polymerase Chain Reaction
RNA, Messenger / analysis,  genetics
Zinc / blood,  metabolism*
Grant Support
Reg. No./Substance:
0/Cation Transport Proteins; 0/DNA Primers; 0/Membrane Proteins; 0/RNA, Messenger; 0/Slc30a1 protein, mouse; 7440-66-6/Zinc; 9038-94-2/Metallothionein

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