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

Sprouty 基因：器官发生的调节因子和 22q11 缺失 (DiGeorge) 综合征的假定修饰因子

• 批准号: G0601104/1
• 负责人: Michiel Basson
• 金额: $ 74.03万
• 依托单位: King's College London
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2007
• 资助国家: 英国
• 起止时间: 2007 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=G0601104%2F1
• 关键词: Sprouty; genes; regulators; organogenesis; putative

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.

我们想要确定Sprouty基因在22q11缺失(DiGeorge)综合征影响的胸腺和其他器官发育中的作用。超过4000名人类婴儿出生时就患有DiGeorge综合征，他们的DNA微小缺失会导致胸腺、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有助于确定22q11缺失中最重要的基因是TBX1。然而，症状的严重程度可能会有很大的差异，这表明缺失区域之外的其他基因也发挥了重要作用。我们最近对小鼠胚胎的研究表明，Sprouty基因控制着DiGeorge综合征许多器官的发育。利用复杂的小鼠遗传学，我们将从特定的组织中移除Sprouty基因，以了解它们在器官发育中的作用。我们将在这种综合征的小鼠模型中测试改变Sprouty基因水平是否可以影响缺陷的严重程度，这将表明Sprouty基因的突变也可以以类似的方式影响人类患者。