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

Nutrition & Metabolism

Edward V Quadros²  Joan Fernandez-Ballart³  Michelle M Murphy³  Shao-Chiang Lai¹  Sílvia Fernàndez-Roig³ 

[1] Departments of Medicine and Cell Biology, SUNY Downstate Medical Center, Brooklyn, NY, USA;Department of Medicine, SUNY Downstate Medical Center, Brooklyn, NY, USA;CIBER Fisiopatología de la Obesidad y Nutrición (CB06/03) Instituto Carlos III, Madrid, 28029, Spain

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

Others  :  815365
DOI  :  10.1186/1743-7075-9-41

 received in 2012-03-22, accepted in 2012-05-18,  发布年份 2012

【 摘 要 】

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.

【 授权许可】

   
2012 Quadros et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

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