Format

Send to

Choose Destination
Hum Mol Genet. 2016 Oct 15;25(20):4369-4375. doi: 10.1093/hmg/ddw267.

Vitamin B12 ameliorates the phenotype of a mouse model of DiGeorge syndrome.

Author information

1
Institute of Genetics and Biophysics, CNR, Via Pietro Castellino, Naples, Italy.
2
IRBM Science Park S.p.A, Via Pontina Km.30.600, Pomezia (RM).
3
Department of Molecular Medicine and Medical Biotechnologies, University Federico II, Naples, Italy

Abstract

Pathological conditions caused by reduced dosage of a gene, such as gene haploinsufficiency, can potentially be reverted by enhancing the expression of the functional allele. In practice, low specificity of therapeutic agents, or their toxicity reduces their clinical applicability. Here, we have used a high throughput screening (HTS) approach to identify molecules capable of increasing the expression of the gene Tbx1, which is involved in one of the most common gene haploinsufficiency syndromes, the 22q11.2 deletion syndrome. Surprisingly, we found that one of the two compounds identified by the HTS is the vitamin B12. Validation in a mouse model demonstrated that vitamin B12 treatment enhances Tbx1 gene expression and partially rescues the haploinsufficiency phenotype. These results lay the basis for preclinical and clinical studies to establish the effectiveness of this drug in the human syndrome.

PMID:
28173146
PMCID:
PMC5409220
DOI:
10.1093/hmg/ddw267
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Silverchair Information Systems Icon for PubMed Central
Loading ...
Support Center