Identification of Mef2c as a common integration site in MuLV-induced myeloid tumors of Irf8^−/− mice. (A) Kaplan-Meier survival curves of Irf8^−/− (n = 47) or Irf8^+/+ (n = 28) B6 mice infected with Mo-MuLV. The log-rank test for comparison of cumulative incidence curves confirmed a significant (P < .001) increase in disease latency in the Irf8-deficient background. The mean survival was 125 (± 6) days and 184 (± 15) days, respectively. (B) Cloning and analysis of sequences flanking retroviral integration sites revealed integrations upstream of the first coding exon of Mef2c, in both 5′ and 3′ orientation to the gene, as indicated. Southern blot analysis of HindIII digested genomic DNA isolated from myeloid tumors originating from MuLV-infected Irf8^−/− mice confirmed disruption of the Mef2c locus, as indicated by arrows. (C) Tumor samples with Mef2c integrations have high levels of Mef2c transcripts. The mean levels of Mef2c transcripts in different tumors (IC) relative to the level in heart tissue were determined by quantitative RT-PCR in 2 independent experiments performed in duplicate. Sequence analysis of RT-PCR fragments demonstrated coding sequences for both α1 and α1-β-γ isoforms in normal BM and tumors, the former being the more prominent form.