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. Author manuscript; available in PMC: 2017 Sep 20.
Published in final edited form as: Nat Genet. 2017 Mar 20;49(5):730–741. doi: 10.1038/ng.3817

Figure 1. A Sleeping Beauty-dependent inactivatable Pten allele for coupled whole-body mutagenesis and tumor suppressor discovery in mice.

Figure 1

(a,b) Transposon-bearing mice used in this study. (a) Single-copy transposon mice (PSB, PtenSBm2/+; Rosa26SB11/+; Blmm3/m3) harbor the novel PtenSBm2 allele, in which Pten exon 5 is flanked by two Sleeping Beauty terminal repeats (SB TRs). This converts the whole cassette into an inactivating transposon which can be mobilized and reintegrated in the genome by the SB transposase, concurrently deleting Pten exon 5. (b) Multiple-copy transposon mice (PISB, PtenSBm2/+; ITP2m; Rosa26SB11/+; Blmm3/m3), carry PtenSBm2 and a new concatemer with ~35 copies of an inactivating transposon (ITP2m) compatible with SB and PiggyBac (PB) transposases. (c) Tumor incidence in PSB (n=59: n♂=38 + n♀=21) and PISB (n=86: n♂=49 + n♀=37) mice. Adenoca., adenocarcinoma; PIN, prostatic intraepithelial neoplasia; Hyp., hyperplasia; Pheo., pheochromocytoma; KA, keratoacanthoma; Adenosq. ca., adenosquamous carcinoma; inf, infiltrating. (d) Photomicrographs of H&E staining in PSB and PISB tumors. Scale bars, 200 µm. (e) Kaplan-Meier survival plot of PSB, PISB, ISB and SB mice. PSB versus PISB (P < 0.0001), ISB (P < 0.0001), SB (P < 0.0001); PISB versus ISB (P < 0.0001), SB (P < 0.0001); ISB versus SB (P = 0.0253); log-rank test. (f) Venn diagram of prostate, breast and skin CIS genes. The top ten most highly mutated genes specific for each tumor type and seven genes found in all three tumor types in both PSB and PISB cohorts are listed. Genes in bold were found in both PSB and PISB screens.