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The transcobalamin receptor knockout mouse: a model for vitamin B 12 deficiency in the central nervous system
Author(s) -
Lai ShaoChiang,
Nakayama Yasumi,
Sequeira Jeffrey M.,
Wlodarczyk Bogdan J.,
Cabrera Robert M.,
Finnell Richard H.,
Bottiglieri Teodoro,
Quadros Edward V.
Publication year - 2013
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.12-219055
Subject(s) - cobalamin , knockout mouse , central nervous system , endocrinology , medicine , receptor , folate receptor , cystathionine beta synthase , biology , homocysteine , methylmalonic acid , gene knockout , vitamin b12 , chemistry , biochemistry , gene , amino acid , methionine , cancer , cancer cell
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.—Lai, S.‐C., Nakayama, Y., Sequeira, J. M., Wlodarczyk, B. J., Cabrera, R. M., Finnell, R. H., Bottiglieri, T., Quadros, E. V. The transcobalamin receptor knockout mouse: a model for vitamin B 12 deficiency in the central nervous system. FASEB J. 27, 2468–2475 (2013). www.fasebj.org