Comparison of Pax6 alpha enhancer Cre-Rblox/lox retinas to Pax6 alpha enhancer Cre-Rblox/lox TET-MYCN retinas at PND12. Mus musculus

The most frequent focal alterations in human retinoblastoma are RB mutation and MYCN amplification. Whether MYCN overexpression drives retinoblastoma has not been assessed in model systems. Here, we show that Rb inactivation collaborates strongly with MYCN overexpression to lead to retinoblastoma in mice. MYCN overexpression in the context of Rb inactivation increased the expression of MYC, E2F and ribosome related gene sets, promoted excessive proliferation and led to retinoblastoma with anaplastic changes. Part of our study compares expression profiles in Rbnull vs Rbnull/MYCN overexpressing retinas collected at 12 days after birth. Overall design: 4 samples of Rb null retina were compared to 4 samples of Rbnull MYCN overexpressing retina, dissected from PND12 peripheral retinas of Pax6alpha-enhancer-Cre;Rblox/lox or Pax6alpha-enhancer-Cre Rosa26LSL-RTTA;TRE-MYCN mice