1. Conditional expression and activation of PDGFRα in the brain of adult mice produces glioblastoma.
Conditional expression and activation of PDGFRα in the brain of adult mice produces glioblastoma. (A) Schematic representation of the Cre–Lox conditional PDGFRα transgene knocked-in the 3′ UTR of the Col1α1 locus. The transcriptional activity of the CAG promoter is prohibited by the presence of a floxed stop cassette (LSL). Expression of PDGFRα is achieved by intracranial stereotactic injections of a Cre recombinase–expressing lentivirus. The virus also contains a DOX-inducible PDGF-A ligand. DOX administration induces expression of PDGF-A and chronic receptor kinase activation. (B) Representative photomicrograph of an H&E-stained formalin-fixed paraformaldehyde embedded section of a PDGF-A;PDGFRα;p53−/− brain tumor. Scale bar, 1 mm. (C) Tumor-free survival (Kaplan–Meier) analysis of cohorts of mice of the indicated genotypes fed a DOX diet of 250 mg/kg. *P < log-rank (Mantel–Cox) test. (D) PDGF-A;PDGFRα;p53−/− tumors have histopathological features of glioblastoma. Representative photomicrographs of formalin-fixed paraformaldehyde embedded tumor sections stained with H&E and immunohistochemical detection of PDGFRα, glial fibrillary acidic protein (GFAP), NeuN, and Ki-67. Scale bars: top row—H&E and PDGFRα 62.5 μm; middle row—GFAP 125 μm, and NeuN 250 μm; and bottom row—H&E and Ki μm. T, tumor; N, normal brain; GFAP, glial fibrillary acidic protein.
Shuang Zhou et al. LSA 2018;1:e
© 2018 zhou et al.