Using the RCAS-TVA system to model human cancer in mice
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Updated: Apr 21, 2026
Identification and Characterization of Metastatic Factors by Gene Transfer into the Novel RIP-Tag; RIP-tva Murine Model
Published on: October 16, 2017
Leanne G Ahronian1, Brian C Lewis1
1Program in Gene Function and Expression, University of Massachusetts Medical School, Worcester, Massachusetts 01605.
Abstract:
For successful infection, avian sarcoma leukosis virus subgroup A (ASLV-A) requires its receptor, tumor virus A (TVA), to be present on the surface of target cells. This is the basis of the RCAS-TVA gene delivery system: Mammalian cells lack the gene encoding TVA and are normally resistant to infection by ASLV; however, transgenic targeting of TVA to specific cell types or tissues in the mouse renders these cells uniquely susceptible to infection by ASLV-A-based RCAS viruses. The RCAS-TVA system is a powerful tool for effectively modeling human tumors, including pancreatic, ovarian, and breast cancers, gliomas, and melanomas. RCAS viruses can deliver cDNAs (≤2.8 kb), as well as short hairpin RNAs (shRNAs), microRNAs (miRNAs), and other noncoding RNAs. Compared with traditional transgenic and knockout mice, the RCAS-TVA system has several strengths. First, virus delivery is generally performed postnatally and results in a relatively low infection rate of target cells; the sporadic postnatal expression of the gene of interest mimics the situation in developing human tumors. Second, a single transgenic mouse line can be used to compare the consequences of specific genes on tumor development, with viruses encoding oncogenes or shRNAs targeting specific tumor suppressor genes. TVA mouse strains can also be easily combined with transgenic, knock-in, and knockout mouse models to study cooperating genetic events.
Insights
The RCAS-TVA system enables targeted gene delivery in mice for cancer modeling. This avian sarcoma leukosis virus subgroup A (ASLV-A) based system allows precise study of tumor development by infecting cells expressing the tumor virus A (TVA) receptor.
Area of Science:
- * Molecular Biology
- * Virology
- * Cancer Research
Background:
- * Avian sarcoma leukosis virus subgroup A (ASLV-A) requires the tumor virus A (TVA) receptor for cell infection.
- * Mammalian cells typically lack TVA, conferring resistance to ASLV-A.
- * Transgenic expression of TVA in mice creates target cells susceptible to ASLV-A-based vectors.
Purpose of the Study:
- * To introduce and detail the RCAS-TVA gene delivery system for modeling human cancers in mice.
- * To highlight the system's utility in studying oncogenesis and gene function in specific cell types.
- * To compare the advantages of RCAS-TVA over traditional transgenic and knockout mouse models.
Main Methods:
- * Engineering mice to express the TVA receptor in specific cell types or tissues.
- * Utilizing ASLV-A-based RCAS viruses for gene delivery (cDNAs, shRNAs, miRNAs) to TVA-expressing cells.
- * Comparing tumor development outcomes in RCAS-TVA models versus conventional genetic models.
Main Results:
- * The RCAS-TVA system effectively models human tumors like pancreatic, ovarian, breast cancers, gliomas, and melanomas.
- * Postnatal, low-efficiency virus delivery mimics sporadic gene expression in developing tumors.
- * Enables comparative studies of oncogenes and tumor suppressor genes in a single transgenic line.
- * Facilitates combination studies with other mouse models to investigate cooperating genetic events.
Conclusions:
- * The RCAS-TVA system is a versatile and powerful tool for preclinical cancer research and modeling.
- * It offers advantages in mimicking tumor development and studying genetic interactions compared to traditional methods.
- * This system facilitates the investigation of gene function and oncogenesis in a targeted and adaptable manner.
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