Conditional Inactivation of Pten with EGFR Overexpression in Schwann Cells Models Sporadic MPNST
Figure 1
Establishing a novel sporadic peripheral nerve sheath tumor (PNST) progression mouse model. (a) Transgenes used to establish the novel sporadic PNST mouse model. Cnp-EGFR consists of the Cnp regulatory elements driving the EGFR gene expression specifically in Schwann cells and/or their precursor cells. Floxed Pten allele consists of the essential exons 4 and 5 of the Pten gene floxed with loxP sites. Dhh-Cre consists of the Dhh regulatory elements driving Cre recombinase to remove the loxP sites and allow for the inactivation of the floxed Pten alleles specifically in Schwann cells and/or their precursor cells. (b) Breeding strategy for generating experimental and control animals. Transgenic mice each carrying a single transgene was bred to obtain doubly transgenic mice Dhh-Cre; mice (Pten-het). Doubly transgenic mice were then bred with remaining transgene to obtain triple transgenic Dhh-Cre; ; Cnp-EGFR mice (Pten-het/C-EGFR). Finally, Pten-het mice were bred with Pten-het/C-EGFR mice to obtain the required experimental and control cohorts. Dhh-Cre; ; Cnp-EGFR (Pten/C-EGFR) and Dhh-Cre; ; Cnp-EGFR (Pten-het/C-EGFR) experimental cohorts. Dhh-Cre; (Pten), Pten-het and Cnp-EGFR (C-EGFR) control cohorts. (c) Kaplan-Meier survival curves of various experimental and control cohorts. Pten dosage augmented the peripheral nervous system phenotype in the context of EGFR overexpression in Schwann cell and/or their precursor cells, resulting in decreased survival. P: log-rank test.
