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Open Access Brief communication

Vitamin B12 deficiency in the brain leads to DNA hypomethylation in the TCblR/CD320 knockout mouse

Sílvia Fernàndez-Roig12, Shao-Chiang Lai3, Michelle M Murphy12, Joan Fernandez-Ballart12 and Edward V Quadros34*

Author Affiliations

1 Area of Preventive Medicine and Public Health, Faculty of Medicine and Health Sciences, Universitat Rovira i Virgili (URV), IISPV, Reus, Spain

2 CIBER Fisiopatología de la Obesidad y Nutrición (CB06/03) Instituto Carlos III, Madrid, 28029, Spain

3 Departments of Medicine and Cell Biology, SUNY Downstate Medical Center, Brooklyn, NY, USA

4 Department of Medicine, SUNY Downstate Medical Center, Brooklyn, NY, USA

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Nutrition & Metabolism 2012, 9:41  doi:10.1186/1743-7075-9-41

Published: 18 May 2012

Abstract

Background

DNA methylation is an epigenetic phenomenon that can modulate gene function by up or downregulation of gene expression. Vitamin B12 and folate pathways are involved in the production of S-Adenosylmethionine, the universal methyl donor.

Findings

Brain vitamin B12 concentration and global DNA methylation was determined in transcobalamin receptor (TCblR/CD320) knock out (KO) (n = 4) and control mice (n = 4) at 20–24 weeks of age. Median [IQR] brain vitamin B12 concentrations (pg/mg) in TCblR/CD320 KO mice compared with control mice was 8.59 [0.52] vs 112.42 [33.12]; p < 0.05. Global DNA methylation levels in brain genomic DNA were lower in TCblR/CD320 KO compared with control mice (Median [IQR]: 0.31[0.16] % vs 0.55[0.15] %; p < 0.05.).

Conclusions

In TCblR/CD320 KO mice, brain vitamin B12 drops precipitously by as much as 90% during a 20 week period. This decrease is associated with a 40% decrease in global DNA methylation in the brain. Future research will reveal whether the disruption in gene expression profiles due to changes in DNA hypomethylation contribute to central nervous system pathologies that are frequently seen in vitamin B12 deficiency.

Keywords:
Vitamin B12 deficiency; Brain; Global DNA methylation; Transcobalamin receptor knock out mice