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Maternofetal transport of vitamin B 12 : role of TCblR/ CD320 and megalin
Author(s) -
Arora Kaveri,
Sequeira Jeffrey M.,
Quadros Edward V.
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.201700025r
Subject(s) - yolk sac , placenta , vitamin b12 , fetus , spinal cord , embryonic stem cell , knockout mouse , endocrinology , biology , medicine , receptor , embryo , microbiology and biotechnology , chemistry , gene , neuroscience , pregnancy , biochemistry , genetics
Vitamin B 12 deficiency 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 B 12 , do not confer embryonic lethality. TC deficiency can produce the hematologic and neurologic complications after birth, whereas TCblR/ CD320 gene defects appear to produce mild metabolic changes. Alternate maternofetal transport mechanisms appear to provide adequate B 12 to the fetus. To understand this mechanism, we evaluated the role of TC, TCblR/ CD320 , and megalin in maternofetal transport of B 12 in a TCblR/ CD320 ‐knockout (KO) mouse. Our results showed high expression of TCblR/ CD320 in 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‐B 12 and TC‐ 57 CoB 12 accumulated 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 B 12 : role of TCblR/ CD320 and megalin. FASEB J. 31, 3098–3106 (2017). www.fasebj.org