IMPC: Analysis of the novel craniocardiac malformation gene Rapgef5

IMPC：新型颅心畸形基因Rapgef5的分析

• 批准号: MR/R014302/1
• 负责人: Karen Liu
• 金额: $ 4.51万
• 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: 2018
• 资助国家: 英国
• 起止时间: 2018 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FR014302%2F1
• 关键词: IMPC; Analysis; novel; craniocardiac; malformation

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.

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健康，我们必须识别和了解出生缺陷的遗传原因，这是改进筛查、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 生成的小鼠模型 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，该信号通路与衰老以及癌症和神经退行性疾病等疾病相关。因此，这种小鼠模型的建立可能为我们提供了解人类出生缺陷以及人类疾病中发生的重要信号传导过程的工具。

项目成果

Expression of the guanine nucleotide exchange factor, RAPGEF5, during mouse and human embryogenesis.

鸟嘌呤核苷酸交换因子 RAPGEF5 在小鼠和人类胚胎发生过程中的表达。

• DOI: http://dx.10.1016/j.gep.2019.119057
• 发表时间: 2019
• 期刊: GEP
• 作者: Alharatani R

A quantitative approach for determining the role of geometrical constraints when shaping mesenchymal condensations.

一种确定间充质凝结成形时几何约束作用的定量方法。

• DOI: http://dx.10.1007/s10544-019-0390-0
• 发表时间: 2019
• 期刊: Biomedical microdevices
• 影响因子: 2.8
• 作者: Onesto V

Induction of Neural Crest Stem Cells From Bardet-Biedl Syndrome Patient Derived hiPSCs.

从 Bardet-Biedl 综合征患者衍生的 hiPSC 中诱导神经嵴干细胞。

• DOI: http://dx.10.3389/fnmol.2019.00139
• 发表时间: 2019
• 期刊: Frontiers in molecular neuroscience
• 作者: Barrell WB