Deletion of apolipoprotein E receptor-2 in mice lowers brain selenium and causes severe neurological dysfunction and death when a low-selenium diet is fed.
Selenoprotein P (Sepp1) is a plasma and extracellular protein that is rich in selenium. Deletion of Sepp1 results in sharp decreases of selenium levels in the brain and testis with dysfunction of those organs. Deletion of Sepp1 also causes increased urinary selenium excretion, leading to moderate depletion of whole-body selenium. The lipoprotein receptor apolipoprotein E receptor-2 (apoER2) binds Sepp1 and facilitates its uptake by Sertoli cells, thus providing selenium for spermatogenesis. Experiments were performed to assess the effect of apoER2 on the concentration and function of selenium in the brain and on whole-body selenium. ApoER2-/- and apoER2+/+ male mice were fed a semipurified diet with selenite added as the source of selenium. ApoER2-/- mice had depressed brain and testis selenium, but normal levels in liver, kidney, muscle, and the whole body. Feeding a selenium-deficient diet to apoER2-/- mice led to neurological dysfunction and death, with some of the characteristics exhibited by Sepp1-/- mice fed the same diet. Thus, although it does not affect whole-body selenium, apoER2 is necessary for maintenance of brain selenium and for prevention of neurological dysfunction and death under conditions of selenium deficiency, suggesting an interaction of apoER2 with Sepp1 in the brain.
Burk
Raymond F
RF
Division of Gastroenterology, Hepatology, and Nutrition, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA. raymond.burk@vanderbilt.edu
Hill
Kristina E
KE
Olson
Gary E
GE
Weeber
Edwin J
EJ
Motley
Amy K
AK
Winfrey
Virginia P
VP
Austin
Lori M
LM
D000818:Animals; D001921:Brain / Q000378:metabolism*; D003643:Death; D004032:Diet / Q000009:adverse effects* / Q000379:methods; D017353:Gene Deletion; D026502:LDL-Receptor Related Proteins; D008297:Male; D044342:Malnutrition / Q000235:genetics* / Q000378:metabolism / Q000401:mortality; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009422:Nervous System Diseases / Q000378:metabolism / Q000401:mortality*; D018110:Receptors, Lipoprotein / Q000172:deficiency* / Q000235:genetics*; D012643:Selenium / Q000172:deficiency* / Q000378:metabolism
D026502:LDL-Receptor Related Proteins; D018110:Receptors, Lipoprotein; C098773:low density lipoprotein receptor-related protein 8; D012643:Selenium