Jerome L A, Papaioannou V E
Department of Genetics and Development, College of Physicians and Surgeons of Columbia University, New York, New York, USA.
Nat Genet. 2001 Mar;27(3):286-91. doi: 10.1038/85845.
The DiGeorge/velocardiofacial syndrome (DGS/VCFS) is a relatively common human disorder, usually associated with deletions of chromosome 22q11. The genetic basis for the wide range of developmental anomalies in the heart, glands and facial structures has been elusive. We have investigated the potential role of one candidate gene, Tbx1, which encodes a transcription factor of the T-box family, by producing a null mutation in mice. We found that mice heterozygous for the mutation had a high incidence of cardiac outflow tract anomalies, thus modeling one of the major abnormalities of the human syndrome. Moreover, Tbx1-/- mice displayed a wide range of developmental anomalies encompassing almost all of the common DGS/VCFS features, including hypoplasia of the thymus and parathyroid glands, cardiac outflow tract abnormalities, abnormal facial structures, abnormal vertebrae and cleft palate. On the basis of this phenotype in mice, we propose that TBX1 in humans is a key gene in the etiology of DGS/VCFS.
迪乔治/心面综合征（DGS/VCFS）是一种相对常见的人类疾病，通常与22号染色体q11区域的缺失有关。心脏、腺体和面部结构中广泛发育异常的遗传基础一直难以捉摸。我们通过在小鼠中产生无效突变，研究了一个候选基因Tbx1的潜在作用，该基因编码T盒家族的一种转录因子。我们发现，该突变的杂合子小鼠心脏流出道异常的发生率很高，从而模拟了人类综合征的主要异常之一。此外，Tbx1基因敲除小鼠表现出广泛的发育异常，几乎涵盖了所有常见的DGS/VCFS特征，包括胸腺和甲状旁腺发育不全、心脏流出道异常、面部结构异常、椎骨异常和腭裂。基于小鼠的这种表型，我们认为人类的TBX1基因是DGS/VCFS病因中的关键基因。
