文章：

用于转化性癌症研究的非生殖系基因工程小鼠模型

Non-germline genetically engineered mouse models for translational cancer research

原文发布日期：2010-07-01

DOI: 10.1038/nrc2877

类型: Review Article

开放获取: 否

要点：

1. Genetically engineered mouse models (GEMMs) have been invaluable in advancing our knowledge of tumour biology. However, accelerated cancer gene discovery through large-scale cancer genomics and an increasing desire to use GEMMs for preclinical therapeutic studies have strained the capacity of germline GEMMs.
2. Non-germline genetic engineering approaches allow for accelerated and flexible genetic manipulation of models.
3. Chimeric models develop tumours in the context of normal stroma, with reduced timelines and mouse housing cost.
4. Transplantation models allow flexible and speedy manipulation of tissue stem and/or progenitor cells with multiple genetic tools (such as knock out, transgenes and RNA interference).
5. Human donor tissue models (or human in mouse models) allow the de novo development of primary human tumours in mouse stroma by manipulating primary human cells.
6. Therapeutic studies in vivo benefit from the wealth of complex GEMM and non-GEMM models to guide drug discovery.

要点翻译：

1. 基因工程小鼠模型（GEMMs）在增进我们对肿瘤生物学的理解方面具有不可估量的价值。然而，通过大规模癌症基因组学加速癌症基因发现，以及越来越多地希望将GEMMs用于临床前治疗研究，已经使得生殖系GEMMs的能力受到限制。
2. 非生殖系基因工程方法能够加速并灵活地对模型进行基因操作。
3. 嵌合模型在正常基质环境中形成肿瘤，缩短了时间并降低了小鼠饲养成本。
4. 移植模型允许利用多种基因工具（如基因敲除、转基因和RNA干扰）对组织干细胞和/或祖细胞进行灵活快速的操作。
5. 人类供体组织模型（或人鼠嵌合模型）通过操作原代人类细胞，能够在小鼠基质中原代发展人类肿瘤。
6. 体内治疗研究受益于丰富的复杂GEMM和非GEMM模型，以指导药物发现。

英文摘要：

Genetically engineered mouse models (GEMMs) of cancer have affected virtually all areas of cancer research. However, the accelerated discovery of new cancer genes emerging from large-scale cancer genomics and new chemical entities pouring from the drug discovery pipeline have strained the capacity of traditional germline mouse models to provide crucial insights. This Review introduces new approaches to modelling cancer, with emphasis on a growing collection of non-germline GEMMs (nGEMMs). These offer flexibility, speed and uniformity at reduced costs, thus paving the way for much needed throughput and practical preclinical therapeutic testing models.

摘要翻译： 

基因工程癌症小鼠模型（GEMMs）几乎影响了癌症研究的所有领域。然而，大规模癌症基因组学揭示的新癌基因以及药物研发管线中涌现的新化学实体，已使传统生殖系小鼠模型在提供关键见解方面的能力不堪重负。本综述介绍了癌症建模的新方法，重点聚焦于日益增多的非生殖系GEMMs（nGEMMs）。这类模型具备灵活性、快速性和一致性，且成本更低，从而为亟需的高通量及实用临床前治疗测试模型铺平了道路。

原文链接：

Non-germline genetically engineered mouse models for translational cancer research