Resource for innovation and application of genetic engineering strategies in embryonic stem cells

这项研究计划的目的是创新实验遗传方法，以研究基因在正常和患病状态下血液发育中的调节和作用。通过使用复杂的基因工程策略，可以通过多种方式改变小鼠胚胎干细胞中的基因（使其失活或修改其功能或表达）。小鼠胚胎干细胞具有无限细胞分裂和分化成几乎所有细胞类型的能力，并且可以创建一个完整的生物体。因此，这些细胞为在细胞和生理水平上研究任何遗传改变的影响提供了一个实验系统。该计划的一个主要重点是通过将人类DNA序列的大区域引入小鼠胚胎干细胞来建立更准确的人类血液疾病模型。这些人类DNA序列可以被改变以概括已知的人类疾病相关突变，因此有可能创建用于评估人类疾病病理和潜在药物治疗的实验动物模型。此外，将基因工程策略应用于人类胚胎干细胞的平行方法正在被遵循。基因改变的人类胚胎干细胞可以在培养皿中分化产生血细胞，因此可以研究和评估基因改变的影响。

The aim of this research programme is to innovate experimental genetic approaches to investigate the regulation and role of genes in blood development in both normal and diseased states. By using sophisticated genetic engineering strategies genes can be altered in numerous ways (to inactivate them or modify their function or expression) in mouse embryonic stem (ES) cells. Mouse ES have the capacity for both unlimited cell division and differentiation into almost all cell types, and can create an entire organism. These cells therefore provide an experimental system for studying the effect of any genetic alterations both at cellular and physiological levels. A major focus of the programme is to build more accurate models of human blood diseases by introducing large regions of human DNA sequence into mouse ES cells. These human DNA sequences can be altered to recapitulate known human disease-associated mutations and thus it is possible to create an experimental animal model for evaluating human disease pathology and potential drug therapies. In addition, a parallel approach is being followed applying genetic engineering strategies to human ES cells. Genetically altered human ES cells can be differentiated in the culture dish to generate blood cells and therefore allow the effects of genetic alterations to be studied and evaluated.