Brain and behavioural anomalies caused by <i>Tbx1</i> haploinsufficiency are corrected by vitamin B12.

ABSTRACT: The brain-related phenotypes observed in 22q11.2 deletion syndrome (DS) patients are highly variable, and their origin is poorly understood. Changes in brain metabolism might contribute to these phenotypes, as many of the deleted genes are involved in metabolic processes, but this is unknown. This study shows for the first time that Tbx1 haploinsufficiency causes brain metabolic imbalance. We studied two mouse models of 22q11.2DS using mass spectrometry, nuclear magnetic resonance spectroscopy, and transcriptomics. We found that Tbx1 ^+/- mice and Df1/⁺ mice, with a multigenic deletion that includes Tbx1, have elevated brain methylmalonic acid, which is highly brain-toxic. Focusing on Tbx1 mutants, we found that they also have

SUBMITTER: Caterino M 

PROVIDER: S-EPMC11579592 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature