Conditional mouse lung cancer models using adenoviral or lentiviral delivery of Cre recombinase

By Michel DuPage, Alison L. Dooley, T. Jacks. Nature Protocols, 2009

867 citations recorded by the source corpus.

The development of animal models of lung cancer is critical to our understanding and treatment of the human disease. Conditional mouse models provide new opportunities for testing novel chemopreventatives, therapeutics and screening methods that are not possible with cultured cell lines or xenograft models. This protocol describes how to initiate tumors in two conditional genetic models of human non-small cell lung cancer (NSCLC) using the activation of oncogenic K-ras alone or in combination with the loss of function of p53. We discuss methods for sporadic expression of Cre in the lungs through engineered adenovirus or lentivirus, and provide a detailed protocol for the administration of the virus by intranasal inhalation or intratracheal intubation. The protocol requires 1–5 min per mouse with an additional 30–45 min to set-up and allow for the recovery of mice from anesthesia. Mice may be analyzed for tumor formation and progression starting 2–3 weeks after infection.

Subfields: Biotechnology, Genetics

View Paper: https://www.semanticscholar.org/paper/6fcb8c648f6b6a9cee67ce4e1a203c3c09272492

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Citations in the corpus

Origins of tumor-associated macrophages and neutrophils (2012, methodology): “adenovirus expressing Cre recombinase by intranasal instillation (18).”
Environment impacts the metabolic dependencies of Ras-driven non-small cell lung cancer (2016, background): “…Cre (Ad5-CMV-Cre) to the lungs of animals harboring conditional KrasLSL-G12D/+; p53loxP/loxP (KP) alleles results in higher grade, metastatic tumors that progress rapidly and cause death within 12–16 weeks (DuPage et al., 2009; Jackson et al., 2001; Jonkers et al., 2001; Tuveson et al., 2004).”
KRAS and YAP1 converge to regulate EMT and tumor survival (2014, background): “We then examined the consequences of Kras inhibition in a well-studied mouse model of lung adenocarcinoma (Tuveson et al., 2004; DuPage et al., 2009).”
CRISPR-Cas9 Knockin Mice for Genome Editing and Cancer Modeling (2014, methodology): “Virus Delivery into the Lung Intranasal and intratracheal delivery of adeno-associated virus were performed accordingly to previously established protocol (DuPage et al., 2009).”