查看文章

Diffuse intrinsic pontine glioma (DIPG) is a universally fatal pediatric cancer arising in the brainstem of children. Their unique brainstem location and pathology, including limited disruption of the blood-brain barrier (BBB), present a significant challenge to treatment. Developing mouse models that accurately reflect the genetic landscape and brainstem location of DIPG will be critical to delineate the role of newly identified mutations in DIPG pathogenesis. Here we describe the efficient generation of DIPG mouse models by targeted transfection of the developing brainstem using in utero electroporation, and characterize the pathological and molecular features associated with PDGFB, Pdgfra, and H3.3 K27M genetic variants. Both PDGFB and Pdgfra^D842V expression, in combination dominant negative Trp53 (DNp53), develop fully penetrate high-grade gliomas that display distinct differences in latency, histology …