Whole mount of adult ear skin as a model to study vascular malformations

Abstract

Abstract Background Genetic analysis in human patients has linked mutations in PIK3CA, the catalytic subunit of PI‐3′Kinase, to sporadic incidences of vascular malformations. Methods We have developed a mouse model with inducible and endothelial‐specific expression of PIK3CAH1047R, resulting in the development of vascular malformations. Systemic induction of this mutation in adult mice results in rapid lethality, limiting our ability to track and study these lesions; therefore, we developed a topical and local induction protocol using the active metabolite of tamoxifen, 4OH‐T, on the ear skin of adults. Results This approach allows us to successfully model the human disease in a mature and established vascular bed and track the development of vascular malformations. To validate the utility of this model, we applied a topical rapamycin ointment, as rapamycin is therapeutically beneficial to patients in clinical trials. We found that the induced ear lesions showed significant attenuation after treatment, which was easily quantified. Conclusions These data collectively provide evidence of a new model to study vascular malformations in adult tissues, which should be particularly useful in environments lacking specialized small‐animal imaging facilities.

Keywords

• animal disease models
• pathological angiogenesis
• PIK3CA
• rapamycin
• vascular malformations