TBX1 is responsible for cardiovascular defects in Velo-Cardio-Facial/DiGeorge syndrome
TBX1 is responsible for cardiovascular defects in Velo-Cardio-Facial/DiGeorge syndrome
复制标题
DOI：
10.1016/s0092-8674(01)00247-1
复制
发表时间：
2001-02-23
期刊：
影响因子：
64.5
通讯作者：
Kucherlapati, R
中科院分区：
文献类型：
--
作者：
Merscher, S;Funke, B;Kucherlapati, R
心面综合征（VCFS）/迪乔治综合征（DGS）是一种人类疾病，其特征是具有包括心血管缺陷在内的多种表型特征。大多数VCFS/DGS患者在22q11的1.5 - 3.0 Mb区域为半合子。为了研究这种疾病的病因，我们采用cre - loxP策略培育出了在与22q11相对应的1.5 Mb缺失区域为半合子的小鼠。这些小鼠表现出显著的围产期致死率，并且具有圆锥动脉干和甲状旁腺缺陷。圆锥动脉干缺陷可通过含有TBX1基因的人类细菌人工染色体（BAC）得到部分挽救。Tbx1基因无效突变的杂合子小鼠会出现圆锥动脉干缺陷。这些结果连同Tbx1的表达模式表明该基因在VCFS/DGS的分子病因中起主要作用。
Velo-cardio-facial syndrome (VCFS)/DiGeorge syndrome (DGS) is a human disorder characterized by a number of phenotypic features including cardiovascular defects. Most VCFS/DGS patients are hemizygous for a 1.5-3.0 Mb region of 22q11. To investigate the etiology of this disorder, we used a cre-loxP strategy to generate mice that are hemizygous for a 1.5 Mb deletion corresponding to that on 22q11. These mice exhibit significant perinatal lethality and have conotruncal and parathyroid defects. The conotruncal defects can be partially rescued by a human BAC containing the TBX1 gene. Mice heterozygous 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.