title: The transcobalamin receptor knockout mouse: a model for vitamin B12 deficiency in the central nervous system.
abstract: 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.
authors: School of Graduate Studies, State University of New York Downstate Medical Center, Brooklyn, NY 11203, USA.
authors: Shao-Chiang
authors: SC
authors: Lai
authors: Yasumi
authors: Y
authors: Nakayama
authors: Jeffrey M
authors: JM
authors: Sequeira
authors: Bogdan J
authors: BJ
authors: Wlodarczyk
authors: Robert M
authors: RM
authors: Cabrera
authors: Richard H
authors: RH
authors: Finnell
authors: Teodoro
authors: T
authors: Bottiglieri
authors: Edward V
authors: EV
authors: Quadros
mesh_terms: D000818:Animals; D001693:Biological Transport, Active; D001921:Brain / Q000378:metabolism; D002493:Central Nervous System Diseases / Q000209:etiology* / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011247:Pregnancy; D011956:Receptors, Cell Surface / Q000172:deficiency* / Q000235:genetics; D014805:Vitamin B 12 / Q000378:metabolism; D014806:Vitamin B 12 Deficiency / Q000209:etiology* / Q000235:genetics / Q000378:metabolism
chemical_list: D011956:Receptors, Cell Surface; C028176:transcobalamin receptor; D014805:Vitamin B 12
keywords: CD320; cellular uptake; homocysteine; methylmalonic acid; nullizygous