Sprouty genes: regulators of organogenesis and putative modifiers of 22q11 deletion (DiGeorge) syndrome

我们希望确定Sprouty基因在22 q11缺失（DiGeorge）综合征中影响的胸腺和其他器官发育中的作用。超过1/4000的人类婴儿出生时患有DiGeorge综合征，其中DNA中的小缺失导致胸腺，甲状旁腺，心脏和中耳等器官发育缺陷。对转基因小鼠胚胎的研究帮助确定了22 q11缺失中最重要的基因Tbx 1。然而，症状的严重程度可能差异很大，这表明缺失区域以外的其他基因也起着重要作用。我们最近对小鼠胚胎的研究表明，Sprouty基因控制着DiGeorge综合征中许多受影响器官的发育。利用复杂的小鼠遗传学，我们将从特定的组织中去除Sprouty基因，以了解它们在器官发育过程中的作用。我们将测试改变Sprouty基因的水平是否会影响这种综合征小鼠模型缺陷的严重程度，这将表明Sprouty基因的突变也可能以类似的方式影响人类患者。

We want to determine the role of Sprouty genes in the development of the thymus and other organs affected in 22q11 deletion (DiGeorge) syndrome.More than 1 in 4000 human babies are born with DiGeorge syndrome where a small deletion in their DNA causes defects in the development of organs such as the thymus, parathyroid, heart and middle ear. Studies in genetically altered mouse embryos have helped identify the most important gene within the 22q11 deletion as Tbx1. However, the severity of symptoms can vary greatly, suggesting that other genes outside the deleted region also play important roles.Our recent studies on mouse embryos have suggested that the Sprouty genes control the development of many of the organs affected in DiGeorge syndrome. Using sophisticated mouse genetics we will remove the Sprouty genes from defined tissues to understand their roles during organ development. We will test whether changing the levels of Sprouty genes can affect the severity of defects in mouse models of this syndrome, which would indicate that mutations in Sprouty genes could also affect human patients in a similar way.