Genetically Engineered Mouse Models for Lung Cancer

Rb1^lox/lox; Trp53^lox/lox (Rb1/Trp53-GEMM) and Rb1^lox/lox; Trp53^lox/lox; Rbl2^lox/lox (Rb1/Trp53/Rbl2-GEMM) have been previously described (14 (link), 16 (link)). Mouse strains with Fgfr1^lox and Fgfr2^lox alleles have been previously described (17 (link), 18 (link)). For tumor induction, lungs of 10-week-old mice, including both male and female mice and littermates, were infected with adenoviral Cre via intratracheal instillation as previously described and mice were aged 6 months (19 (link)). For allograft experiment, we inject 5.0×10⁵ control or Fgfr1-preSC in the flanks of nude mice (Foxn1^nu/nu; Envigo) and 1.0×10⁶Fgfr1^lox/loxRb1/Trp53/Rbl2 murine cells infected with Ad-Cre in the flanks of B6/129S F1 hybrid mice (Jackson Laboratory). To induce FGFR1 expression in Fgfr1-preSC following implantation, mice were fed doxycycline diet (625mg/kg, Envigo). Mice were maintained according to guidelines from the National Institutes of Health. Animal procedures were approved by the Institutional Animal Care and Use Committee at the University of Virginia.