Deletion of selenoprotein P alters distribution of selenium in the mouse.
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.
Hill
Kristina E
KE
Division of Gastroenterology, Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA.
Zhou
Jiadong
J
McMahan
Wendy J
WJ
Motley
Amy K
AK
Atkins
John F
JF
Gesteland
Raymond F
RF
Burk
Raymond F
RF
D000818:Animals; D001921:Brain / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D017353:Gene Deletion; D005822:Genetic Vectors; D005838:Genotype; D005979:Glutathione Peroxidase / Q000378:metabolism; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008957:Models, Genetic; D009206:Myocardium / Q000378:metabolism; D010641:Phenotype; D011506:Proteins / Q000235:genetics*; D012643:Selenium / Q000378:metabolism* / Q000494:pharmacology; D051149:Selenoprotein P; D051140:Selenoproteins; D013737:Testis / Q000378:metabolism; D013997:Time Factors
D011506:Proteins; D051149:Selenoprotein P; D051140:Selenoproteins; D005979:Glutathione Peroxidase; D012643:Selenium