Document Detail

Deletion of selenoprotein P alters distribution of selenium in the mouse.
MedLine Citation:
PMID:  12574155     Owner:  NLM     Status:  MEDLINE    
Selenoprotein P (Se-P) contains most of the selenium in plasma. Its function is not known. Mice with the Se-P gene deleted (Sepp(-/-)) were generated. Two phenotypes were observed: 1) Sepp(-/-) mice lost weight and developed poor motor coordination when fed diets with selenium below 0.1 mg/kg, and 2) male Sepp(-/-) mice had sharply reduced fertility. Weanling male Sepp(+/+), Sepp(+/-), and Sepp(-/-) mice were fed diets for 8 weeks containing <0.02-2 mg selenium/kg. Sepp(+/+) and Sepp(+/-) mice had similar selenium concentrations in all tissues except plasma where a gene-dose effect on Se-P was observed. Liver selenium was unaffected by Se-P deletion except that it increased when dietary selenium was below 0.1 mg/kg. Selenium in other tissues exhibited a continuum of responses to Se-P deletion. Testis selenium was depressed to 19% in mice fed an 0.1 mg selenium/kg diet and did not rise to Sepp(+/+) levels even with a dietary selenium of 2 mg/kg. Brain selenium was depressed to 43%, but feeding 2 mg selenium/kg diet raised it to Sepp(+/+) levels. Kidney was depressed to 76% and reached Sepp(+/+) levels on an 0.25 mg selenium/kg diet. Heart selenium was not affected. These results suggest that the Sepp(-/-) phenotypes were caused by low selenium in testis and brain. They strongly suggest that Se-P from liver provides selenium to several tissues, especially testis and brain. Further, they indicate that transport forms of selenium other than Se-P exist because selenium levels of all tissues except testis responded to increases of dietary selenium in Sepp(-/-) mice.
Kristina E Hill; Jiadong Zhou; Wendy J McMahan; Amy K Motley; John F Atkins; Raymond F Gesteland; Raymond F Burk
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.     Date:  2003-02-06
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  278     ISSN:  0021-9258     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2003 Apr 
Date Detail:
Created Date:  2003-04-14     Completed Date:  2003-05-22     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  13640-6     Citation Subset:  IM    
Division of Gastroenterology, Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA.
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MeSH Terms
Brain / metabolism
Dose-Response Relationship, Drug
Gene Deletion*
Genetic Vectors
Glutathione Peroxidase / metabolism
Kidney / metabolism
Liver / metabolism
Mice, Inbred C57BL
Mice, Knockout
Mice, Transgenic
Models, Genetic
Myocardium / metabolism
Proteins / genetics*
Selenium / metabolism*,  pharmacology
Selenoprotein P
Testis / metabolism
Time Factors
Grant Support
Reg. No./Substance:
0/Proteins; 0/Selenoprotein P; 0/Selenoproteins; 7782-49-2/Selenium; EC Peroxidase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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