Alb-Cre+/MYC+ Mice

Catalog Number: C001339

Strain Name: C57BL/6JCya-Igs2em1(CAG-LSL-HA tag-hMYC-IRES-eGFP)Tg(Alb-Cre)/Cya

Genetic Background: C57BL/6JCya

 

Strain Description

The MYC oncogene family comprises regulatory genes and proto-oncogenes that encode transcription factors, involved in various cellular processes such as the cell cycle, apoptosis, DNA repair, and metabolism. Members include c-Myc (MYC), l-Myc (MYCL), and n-Myc (MYCN). c-Myc (MYC) is a basic helix-loop-helix leucine zipper (bHLHZip) transcription factor, which forms heterodimers with Max protein to bind DNA and regulate the expression of approximately 15% of genes, thereby participating in key cellular processes such as cell proliferation, apoptosis, DNA repair, and metabolism. In many cancers, c-Myc is overexpressed, leading to uncontrolled cell proliferation and tumor growth, such as in Burkitt's lymphoma where c-Myc gene rearrangement is common. Dysregulation of the MYC oncogene plays a crucial role in tumorigenesis, predominantly through transcriptional dysregulation resulting in overexpression of c-Myc protein.

Alb-Cre+/MYC+ mice are generated by crossing H11-CAG-LSL-hMYC-IRES-EGFP mice (Catalog Number: C001338), which conditionally express the human c-Myc oncogene, with Alb-Cre mice that express Cre recombinase specifically in hepatocytes under the control of the Alb promoter. The Cre-mediated recombination results in the deletion of the transcriptional stop sequence (Loxp-Stop-Loxp, LSL) in H11-CAG-LSL-hMYC-IRES-EGFP mice, leading to overexpression of the MYC oncogene in the liver and subsequent carcinogenesis. This model, therefore, spontaneously develops liver cancer with an early onset.

Strain Strategy

H11-CAG-LSL-hMYC-IRES-EGFP mice (Catalog Number: C001338) were constructed by integrating the CAG-LSL-hMYC-IRES-EGFP expression element into the H11 safe harbor locus of the mouse genome. By crossing these mice with liver-specific Alb-Cre mice, a model overexpressing the human MYC CDS in the liver, i.e., Alb-Cre+/MYC+ mice (Catalog Number: C001339), was generated.

 

Strain Application

  • Liver Cancer Research: The model overexpresses the MYC oncogene in the liver, spontaneously developing liver cancer, thus serving as a tool to study the mechanisms of liver cancer initiation and progression.
  • Drug Screening and Evaluation: Utilized to assess the efficacy of new anti-liver cancer drugs and therapeutic strategies, particularly those targeting MYC-driven tumors.
  • Gene Function Studies: Investigates the role of the MYC gene in hepatocytes and its involvement in tumor formation.
  • Transcriptional Regulation Studies: Explores the mechanisms of MYC in transcriptional regulation and its interactions with other genes and signaling pathways.

 

Validation Data

1. Survival Curve

Figure 1. Survival curve of Alb-Cre+/MYC+ mice. The data show that approximately 50% of Alb-Cre+/MYC+ mice die around 6 weeks of age.

2. Liver Tumor Observation

Figure 2. Comparison of liver morphology between wild-type (WT) mice and Alb-Cre+/MYC+ mice. Results show that by 4 weeks of age, Alb-Cre+/MYC+ female mice exhibit visible white nodules or prominent tumors, with individual variation in tumor development and disease severity compared to normal WT mice.

3. Liver H&E Staining

Figure 3. H&E staining of liver tissue from WT and Alb-Cre+/MYC+ mice. Histological analysis shows normal liver with no significant lesions in WT mice, while 4-week-old Alb-Cre+/MYC+ female mice develop multifocal cholangiocarcinoma, characterized by glandular structures, mucin presence, minimal connective tissue, and strong basophilic cells lining the glands. Significant infiltration into the surrounding liver parenchyma, metastasis, and solid tumor masses are observed, resembling mixed hepatobiliary carcinoma, predominantly cholangiocarcinoma.