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

Abstract

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.

• Authors: Gabriella Lania, Alberto Bresciani, Monica Bisbocci, Alessandra Francone, Vincenza Colonna, Sergio Altamura, Antonio Baldini
• Journal: Human molecular genetics (Hum Mol Genet) Vol. 25 Issue 20 Pg. 4369-4375 (10 15 2016) ISSN: 1460-2083 [Electronic] England
• PMID: 28173146 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• T-Box Domain Proteins
• Tbx1 protein, mouse
• Vitamin B 12

Topics

• Animals
• DiGeorge Syndrome (drug therapy, embryology, metabolism)
• Disease Models, Animal
• Gene Expression Regulation, Developmental
• Haploinsufficiency
• High-Throughput Screening Assays
• Mice
• Mutation
• T-Box Domain Proteins (drug effects, genetics)
• Vitamin B 12 (pharmacology, therapeutic use)