Vitamin B12 ameliorates the phenotype of a mouse model of DiGeorge syndrome.
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.
Institute of Genetics and Biophysics, CNR, Via Pietro Castellino, Naples, Italy.
Gabriella
G
Lania
IRBM Science Park S.p.A, Via Pontina Km.30.600, Pomezia (RM).
Alberto
A
Bresciani
IRBM Science Park S.p.A, Via Pontina Km.30.600, Pomezia (RM).
Monica
M
Bisbocci
IRBM Science Park S.p.A, Via Pontina Km.30.600, Pomezia (RM).
Alessandra
A
Francone
Institute of Genetics and Biophysics, CNR, Via Pietro Castellino, Naples, Italy.
Vincenza
V
Colonna
IRBM Science Park S.p.A, Via Pontina Km.30.600, Pomezia (RM).
Sergio
S
Altamura
Department of Molecular Medicine and Medical Biotechnologies, University Federico II, Naples, Italy
Antonio
A
Baldini
D000818:Animals; D004062:DiGeorge Syndrome / Q000188:drug therapy* / Q000196:embryology / Q000378:metabolism; D004195:Disease Models, Animal; D018507:Gene Expression Regulation, Developmental; D057895:Haploinsufficiency; D057166:High-Throughput Screening Assays; D051379:Mice; D009154:Mutation; D020825:T-Box Domain Proteins / Q000187:drug effects* / Q000235:genetics; D014805:Vitamin B 12 / Q000494:pharmacology* / Q000627:therapeutic use
D020825:T-Box Domain Proteins; C491573:Tbx1 protein, mouse; D014805:Vitamin B 12