A method to establish a c-Myc transgenic mouse model of hepatocellular carcinoma

Yan Mei,Chao Zhou,Chao-Yong Liang,Guan-Ming Lu,Mu-Sheng Zeng,Jin-Jin Wang,Guo-Kai Feng

doi:10.1016/j.mex.2020.100921

Abstract

Hepatocellular carcinoma (HCC) remains one of the most lethal malignant cancers worldwide. HCC mouse models are widely used to explore the molecular pathogenesis of HCC and to test novel drug candidates.The advantages of this mouse model are as follows:•This method developed a H11LNL-Myc knock-in HCC mouse model by crossing H11LNL-Myc heterozygous mice with (albumin (Alb))-cre transgenic mice to generate c-Myc/Alb-cre double positive mice.•The c-Myc/Alb-cre double-positive mice exhibited a typical HCC phenotype, and showed accelerated tumor initiation and rapid HCC progression. Early stage HCC tumors (2–3 mm in diameter) were observed in male mice at the age of 47 days and in female mice at the age of 60 days.•Approximately 3 months later, the HCC tumors had progressed to a late stage (> 1 cm in diameter), and 100% of the male and female mice had HCC.

Highlights

Hepatocellular carcinoma (HCC) is estimated to be the fifth most common cause of cancer and the second leading cause of cancer-related deaths, and its incidence is increasing worldwide [1]
C-Myc is overexpressed in up to 70% of patients with viral and alcohol-related HCC [2]. c-Myc functions mainly as a transcription factor that coordinates many biological processes, and c-Myc activation contributes to autonomous proliferation and growth [3], inhibition of differentiation [4], and induction of genomic destabilization [5]. c-Myc coordinates the transcription of thousands of protein-coding genes, microRNAs, and long noncoding RNAs [3,6,7]
While the Cre-loxP system is predominantly used for targeted gene deletion, it induces sitespecific gene insertion, which is mediated by a Cre-loxP-carrying lentiviral vector [9]

Summary

Method Article

A method to establish a c-Myc transgenic mouse model of hepatocellular carcinoma. HCC mouse models are widely used to explore the molecular pathogenesis of HCC and to test novel drug candidates. The advantages of this mouse model are as follows:. Method name: c-Myc knock-in mouse model Keywords: c-Myc, Transgenic mouse model, Hepatocellular carcinoma, Knock-in Article history: Received 30 August 2019; Accepted 9 May 2020; Available online 17 May 2020. Subject area: More specific subject area: Method name: Name and reference of original method: Resource availability: Biochemistry, Genetics and Molecular Biology Developing a H11LNL-Myc knock-in HCC mouse model c-Myc knock-in mouse model Murakami H., 1993.

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