title: Maternofetal transport of vitamin B12: role of TCblR/CD320and megalin.
abstract: Vitamin B12deficiency causes megaloblastic anemia and neurologic disorder in humans. Gene defects of transcobalamin (TC) and the transcobalamin receptor (TCblR), needed for cellular uptake of the TC-bound B12, do not confer embryonic lethality. TC deficiency can produce the hematologic and neurologic complications after birth, whereas TCblR/CD320gene defects appear to produce mild metabolic changes. Alternate maternofetal transport mechanisms appear to provide adequate B12to the fetus. To understand this mechanism, we evaluated the role of TC, TCblR/CD320, and megalin in maternofetal transport of B12in a TCblR/CD320-knockout (KO) mouse. Our results showed high expression of TCblR/CD320in the labyrinth of the placenta, embryonic brain, and spinal column in wild-type (WT) mice. Megalin expression was about the same in both WT and KO mouse visceral yolk sac, brain, and spinal column. Megalin mRNA was down-regulated in the KO embryonic spinal cord (SC) and kidneys. Megalin expression remained unaltered in adult WT and KO mouse brain, SC, and kidneys. Injected dsRed-TC-B12and TC-57CoB12accumulated in the visceral yolk sac of KO mice where megalin is expressed and provides an alternate mechanism for the maternofetal transport of Cbl during fetal development.-Arora, K., Sequeira, J. M., Quadros, E. V. Maternofetal transport of vitamin B12: role of TCblR/CD320and megalin.
authors.affiliation: Department of Cell Biology, School of Graduate Studies, State University of New York (SUNY) Downstate Medical Center, Brooklyn, New York, USA.
authors.forename: Kaveri
authors.initials: K
authors.lastname: Arora
authors.affiliation: Department of Medicine, SUNY Downstate Medical Center, Brooklyn, New York, USA.
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Sequeira
authors.affiliation: Department of Medicine, SUNY Downstate Medical Center, Brooklyn, New York, USA edward.quadros@downstate.edu.
authors.forename: Edward V
authors.initials: EV
authors.lastname: Quadros
mesh_terms: D000818:Animals; D001692:Biological Transport; D002490:Central Nervous System / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology*; D007668:Kidney / Q000378:metabolism; D026561:Low Density Lipoprotein Receptor-Related Protein-2 / Q000235:genetics / Q000378:metabolism*; D008431:Maternal-Fetal Exchange / Q000502:physiology*; D051379:Mice; D010920:Placenta / Q000378:metabolism; D011247:Pregnancy; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000502:physiology*; D014018:Tissue Distribution; D014805:Vitamin B 12 / Q000378:metabolism*; D015017:Yolk Sac / Q000378:metabolism
chemical_list: D026561:Low Density Lipoprotein Receptor-Related Protein-2; C055127:Lrp2 protein, mouse; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; C028176:transcobalamin receptor; D014805:Vitamin B 12
keywords: brain; cobalamin; fetal development; placenta; yolk sac