The transcobalamin receptor knockout mouse: a model for vitamin B12 deficiency in the central nervous system

FASEB J. 2013 Jun;27(6):2468-75. doi: 10.1096/fj.12-219055. Epub 2013 Feb 21.


The membrane receptor (TCblR/CD320) for transcobalamin (TC)-bound cobalamin (Cbl) facilitates the cellular uptake of Cbl. A genetically modified mouse model involving ablation of the CD320 gene was generated to study the effects on cobalamin homeostasis. The nonlethal nature of this knockout and the lack of systemic cobalamin deficiency point to other mechanisms for cellular Cbl uptake in the mouse. However, severe cobalamin depletion in the central nervous system (CNS) after birth (P<0.01) indicates that TCblR is the only receptor responsible for Cbl uptake in the CNS. Metabolic Cbl deficiency in the brain was evident from the increased methylmalonic acid (P<0.01-0.04), homocysteine (P<0.01), cystathionine (P<0.01), and the decreased S-adenosylmethionine/S-adenosyl homocysteine ratio (P<0.01). The CNS pathology of Cbl deficiency seen in humans may not manifest in this mouse model; however, it does provide a model with which to evaluate metabolic pathways and genes affected.

Keywords: CD320; cellular uptake; homocysteine; methylmalonic acid; nullizygous.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Biological Transport, Active
  • Brain / metabolism
  • Central Nervous System Diseases / etiology*
  • Central Nervous System Diseases / genetics
  • Central Nervous System Diseases / metabolism
  • Disease Models, Animal
  • Female
  • Humans
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Pregnancy
  • Receptors, Cell Surface / deficiency*
  • Receptors, Cell Surface / genetics
  • Vitamin B 12 / metabolism
  • Vitamin B 12 Deficiency / etiology*
  • Vitamin B 12 Deficiency / genetics
  • Vitamin B 12 Deficiency / metabolism


  • Receptors, Cell Surface
  • transcobalamin receptor
  • Vitamin B 12