TBX1 is responsible for cardiovascular defects in Velo-Cardio-Facial/DiGeorge syndrome

Velo-cardio-facial syndrome (VCFS)/DiGeorge syndrome (DGS) is a human disor der characterized by a number of phenotypic features including cardiovascul ar defects. Most VCFS/DGS patients are hemizygous for a 1.5-3.0 Mb region o f 22q11. To investigate the etiology of this disorder, we used a cre-loxP s trategy to generate mice that are hemizygous for a 1.5 Mb deletion correspo nding to that on 22q11. These mice exhibit significant perinatal lethality and have conotruncal and parathyroid defects. The conotruncal defects can b e partially rescued by a human BAC containing the TBX1 gene. Mice heterozyg ous for a null mutation in Tbx1 develop conotruncal defects. These results together with the expression patterns of Tbx1 suggest a major role for this gene in the molecular etiology of VCFS/DGS.