IMPC: Analysis of the novel craniocardiac malformation gene Rapgef5

出生缺陷是英国和欧洲婴儿死亡的主要原因。其中，先天性颅面和心脏畸形是最常见的，心脏异常是婴儿死亡和发病的主要原因。如果我们要改善患者的福祉，我们必须确定和了解出生缺陷的遗传原因，作为改善筛查，遗传咨询和个性化治疗策略的关键第一步。在心脏异常患者中鉴定出人类RAPGEF5后，我们现在需要建立一个哺乳动物模型，以便更好地了解该基因的潜在生物学作用。该泵启动项目将建立IMPC产生的小鼠模型Rapgef5。除了作为出生缺陷基因的作用外，Rapgef5似乎在Wnt信号通路中也很重要，Wnt信号通路与衰老以及癌症和神经变性等疾病有关。因此，这种小鼠模型的建立可能为我们提供一种工具，以了解人类出生缺陷以及发生在人类疾病中的重要信号传导过程。

Birth defects are the major cause of infant mortality in the UK and in Europe. Of these, congenital craniofacial and cardiac malformations are amongst the most common with heart anomalies as the leading cause of infant mortality and morbidity. If we are to improve patient well being, we must identify and understand the genetic causes of birth defects as a critical first step towards improved screening, genetic counselling and personalised treatment strategies. Having identified human RAPGEF5 in patients with heart anomalies, we now need to establish a mammalian model, in order to better understand the underlying biological roles for the gene. This pump-priming project will establish an IMPC-generated mouse model Rapgef5. In addition to its role as a birth defect gene, Rapgef5 also seems to be important in the Wnt signalling pathway, which is associated with aging, and with disorders such as cancer and neurodegeneration. Therefore, establishment of this mouse model may provide us with a tool to understand human birth defects as well as important signalling processes that occur in human disease.