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J. Biol. Chem., Vol. 278, Issue 16, 13640-13646, April 18, 2003

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Deletion of Selenoprotein P Alters Distribution of Selenium in the Mouse^*

Kristina E. Hill, Jiadong Zhou^§, Wendy J. McMahan, Amy K. Motley, John F. Atkins^§¶, Raymond F. Gesteland^§, and Raymond F. Burk^**

From the  Division of Gastroenterology, Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee 37232 and ^§ Eccles Institute of Human Genetics, The University of Utah, Salt Lake City, Utah 84112

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.

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