The resulting p53/Hells DKO (Osx-cre p53lox/lox; Hellslox/lox) and p53/Rb1/Hells triple knockout (TKO; Osx-cre p53lox/lox; Rb1lox/lox; Hellslox/lox) were compared to their corresponding littermate controls (p53 cKO and p53/Rb1 DKO, respectively) for the assessment of the role of HELLS in tumor initiation and promotion during osteosarcoma development. The gene discussed is SP7; the disease is osteosarcoma.