Maternofetal transport of vitamin B12: role of TCblR/CD320 and megalin [Research]

Vitamin B₁₂ 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 B₁₂, 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 B₁₂ to the fetus. To understand this mechanism, we evaluated the role of TC, TCblR/CD320, and megalin in maternofetal transport of B₁₂ 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 SC and kidneys. Megalin expression remained unaltered in adult WT and KO mouse brain, spinal cord (SC), and kidneys. Injected dsRed-TC-B₁₂ and TC-⁵⁷CoB₁₂ accumulated in the visceral yolk sac of KO mouse 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/CD320 and megalin.

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