Maternofetal transport of vitamin B 12 : role of TCblR/ CD320 and megalin

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