The PAX7::FOXO1 subtype of alveolar rhabdomyosarcoma (aRMS) is both understudied and an unmet clinical need. The biology of PAX7::FOXO1 aRMS is significantly different than PAX3::FOXO1 aRMS, presenting an opportunity to gain biological, clinical and therapeutic insights by murine genetic modeling of Pax7::Foxo1 for comparison to the existing conditional genetic mouse model of Pax3::Foxo1 aRMS. Using gene targeting, a mouse strain harboring a Cre-LoxP activated conditional knock-in of Pax7::Foxo1 targeted to the murine Pax7 locus has been generated. Activation of the conditional knock-in of Pax7::Foxo1 allele in the prenatal Pax7 lineage recapitulates the birth defects (stunting and maxillofacial deformities) known for the conditional knock-in of Pax3::Foxo1 allele. Activation of the conditional knock-in of Pax7::Foxo1 allele in the prenatal Myf6 lineage is viable, fertile, and results in ongoing expression from Pax7 promoter in myofibers. This mouse strain is a resource for the rhabdomyosarcoma research community to explore lineage (cell) of origin, to define sufficiency for tumor initiation or the necessity of cooperative tumor initiating mutations, to uncover the biology of the PAX7::FOXO1 subtype of alveolar rhabdomyosarcoma, and to test therapies including immunotherapies.
Askew et al. (Fri,) studied this question.