How is cancer induced in mice for research purposes? - briefly
Researchers induce tumors in mice by introducing genetically engineered cells, carcinogenic chemicals, viral vectors, or CRISPR‑mediated gene edits that activate oncogenes or inactivate tumor suppressors. These approaches generate reproducible malignancies that closely model human cancer for preclinical studies.
How is cancer induced in mice for research purposes? - in detail
Researchers induce malignant growths in laboratory mice through several well‑characterized approaches, each tailored to the biological question and tumor type under investigation.
Genetically engineered models create oncogenic alterations within the mouse genome. Transgenic lines express oncogenes (e.g., MYC, KRAS^G12D) under tissue‑specific promoters, producing spontaneous tumors in the targeted organ. Conditional systems, such as Cre‑Lox recombination, allow temporal control: a Cre‑expressing virus or drug‑inducible Cre allele activates the oncogene at a chosen developmental stage, providing precise onset of disease. Knock‑in or knock‑out strategies delete tumor suppressor genes (e.g., p53, PTEN), increasing susceptibility to neoplasia. CRISPR/Cas9 delivery via plasmid, viral vector, or ribonucleoprotein complexes introduces point mutations or chromosomal rearrangements directly into somatic cells, generating rapid, mosaic tumor models.
Chemical carcinogenesis employs mutagenic agents administered systemically or locally. 7,12‑Dimethylbenz[a]anthracene (DMBA) applied topically induces skin papillomas that progress to squamous cell carcinoma. N‑Nitrosodiethylamine (DEN) injected intraperitoneally produces hepatocellular carcinoma after repeated dosing. Protocols specify concentration, frequency, and age of the animal to achieve reproducible tumor latency. Chemical exposure often requires a promotional agent, such as 12‑O‑tetradecanoylphorbol‑13‑acetate (TPA), to enhance tumor development.
Radiation‑induced models expose mice to ionizing radiation (X‑ray, γ‑ray, or neutron beams) at defined doses (typically 2–8 Gy) targeting specific tissues. Whole‑body irradiation predisposes to lymphoid malignancies, whereas focal irradiation of the brain or lung initiates gliomas or adenocarcinomas, respectively. Dose fractionation and shielding parameters are calibrated to balance tumor induction against animal welfare.
Transplantation techniques introduce established tumor cells into immunocompetent or immunodeficient hosts. Syngeneic transplantation injects murine cancer cell lines (e.g., B16 melanoma, LLC lung carcinoma) into genetically matched mice, preserving an intact immune environment. Xenograft models implant human cancer cells or patient‑derived tumor fragments into nude, SCID, or NSG mice; these hosts lack functional T, B, and NK cells, allowing growth of human tissue. Orthotopic implantation places cells into the organ of origin, improving relevance to metastatic behavior.
Viral oncogenesis exploits oncogenic viruses to deliver tumor‑inducing genes. Retroviral vectors encode activated oncogenes and integrate into host DNA after systemic injection. Lentiviral particles transduce dividing and non‑dividing cells, enabling stable expression of oncogenic drivers. Adenoviral or adeno‑associated virus vectors provide transient expression, useful for studying early tumor initiation events.
Each method requires careful selection of mouse strain, age, sex, and housing conditions to minimize variability. Monitoring involves palpation, imaging (ultrasound, MRI, PET), and histopathological analysis to confirm tumor type, grade, and progression. Ethical oversight mandates adherence to institutional animal care guidelines, including humane endpoints and analgesia protocols.