使用 CRISPR-Cas9 生成人源 HCC 小鼠模型和癌症驱动突变的方案。
Protocol for generation of humanized HCC mouse model and cancer-driver mutations using CRISPR-Cas9.
机构信息
Departments of Molecular Microbiology and Immunology, University of Southern California, Los Angeles, Los Angeles, CA, USA.
Departments of Pathology, University of Southern California, Los Angeles, Los Angeles, CA, USA; Southern California Research Center for ALPD and Cirrhosis, Los Angeles, CA, USA.
出版信息
STAR Protoc. 2023 Dec 15;4(4):102389. doi: 10.1016/j.xpro.2023.102389. Epub 2023 Dec 8.
We detail procedures for generating a humanized mouse model of hepatocellular carcinoma (HCC) recapitulating genetic mutations associated with metabolic liver diseases (MLD). We humanized liver parenchymal, non-parenchymal, and hematopoietic cells. We employed CRISPR-Cas9-based ARID1A knockout and constitutively active CTNNB1 knockin combined with an alcohol Western diet to generate cancer-driver mutations commonly found in MLD-HCC patients. This HCC model facilitates the study of tumor-promoting gene-environment interactions. For complete details on the use and execution of this protocol, please refer to Yeh et al..
我们详细介绍了生成肝细胞癌 (HCC) 人源化小鼠模型的步骤，该模型可重现与代谢性肝病 (MLD) 相关的遗传突变。我们对肝实质细胞、非实质细胞和造血细胞进行了人源化处理。我们采用基于 CRISPR-Cas9 的 ARID1A 敲除和 CTNNB1 组成型激活的 knockin 方法，结合酒精西方饮食，生成 MLD-HCC 患者中常见的癌症驱动基因突变。该 HCC 模型有利于研究促进肿瘤发生的基因-环境相互作用。如需详细了解本方案的使用和实施，请参考 Yeh 等人的研究。
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