Maternofetal transport of vitamin B: role of TCblR/ and megalin.

Vitamin B 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, do not confer embryonic lethality. TC deficiency can produce the hematologic and neurologic complications after birth, whereas TCblR/ gene defects appear to produce mild metabolic changes. Alternate maternofetal transport mechanisms appear to provide adequate B to the fetus. To understand this mechanism, we evaluated the role of TC, TCblR/, and megalin in maternofetal transport of B in a TCblR/-knockout (KO) mouse. Our results showed high expression of TCblR/ 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 and TC-CoB 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: role of TCblR/ and megalin.