ISOLATION AND CHARACTERIZATION OF A GENE FROM THE DIGEORGE CHROMOSOMAL REGION HOMOLOGOUS TO THE MOUSE TBX1 GENE

DiGeorge syndrome, velocardiofacial syndrome, conotruncal anomaly face syndrome, and isolated and familial forms of conotruncal cardiac defe ats have been associated with deletions of chromosomal region 22q11.2. This report describes the identification, cloning, and characterizati on of the human TBX1 gene, which maps to the center of the DiGeorge ch romosomal region. Further, we have extended the mouse cDNA sequence to permit comparisons between human and mouse Tbx1. TBX1 is a member of a]phylogenetically conserved family of genes that share a common DNA-b inding domain, the T-box. T-box genes are transcription factors involv ed in the regulation of developmental processes. There is 98% amino ac id identity between human and mouse TBX1 proteins overall, and within the T-box domain, the proteins are identical except for two amino acid s. Expression of human TBX1 in adult and fetal tissues, as determined by Northern blot analysis, is similar to that found in the mouse. Addi tionally, using 3'RACE, we obtained a differentially spliced message i n adult skeletal muscle. Mouse Tbx1 has been previously shown to be ex pressed during early embryogenesis in the pharyngeal arches, pouches, and otic vesicle. Later in development, expression is seen in the vert ebral column and tooth bud. Thus, human TBX1 is a candidate for some o f the features seen in the 22q11 deletion syndrome. (C) 1997 Academic Press.