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Background  DNA methylation is an epigenetic phenomenon that can modulate gene function by up or downregulation of gene expression. Vitamin B 12  and folate pathways are involved in the production of S-Adenosylmethionine, the universal methyl donor.    Findings  Brain vitamin B 12  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 B 12  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 B 12  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 B 12  deficiency.

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