Brain and behavioural anomalies caused byTbx1haploinsufficiency are corrected by vitamin B12

• DOI: 10.26508/lsa.202403075
• Publication Date: 2024-11-20T16:45:13Z
• Authors: Marianna Caterino; Debora Paris; Giulia Torromino; Michele Costanzo; Gemma Flore; Annabella Tramice; Elisabetta Golini; Silvia Mandillo; Diletta Cavezza; Claudia Angelini; Margherita Ruoppolo; Andrea Motta; Elvira De Leonibus; Antonio Baldini; Elizabeth Illingw...; Gabriella Lania
• Keywords: Haploinsufficiency; TBX1; Metabolome

The brain-related phenotypes observed in 22q11.2 deletion syndrome (DS) patients are highly variable, and their origin is poorly understood. Changes brain metabolism might contribute to these phenotypes, as many of the deleted genes involved metabolic processes, but this unknown. This study shows for first time that Tbx1 haploinsufficiency causes imbalance. We studied two mouse models 22q11.2DS using mass spectrometry, nuclear magnetic resonance spectroscopy, transcriptomics. found +/− mice Df1/ + mice, with a multigenic includes , have elevated methylmalonic acid, which brain-toxic. Focusing on mutants, we they also more general metabolomic imbalance affects key pathways, such glutamine–glutamate fatty acid metabolism. provide transcriptomic evidence genotype–vitamin B12 treatment interaction. In addition, vitamin rescued behavioural anomaly mice. Further studies will be required establish whether specific metabolites affected by potential biomarkers disease status patients.