Survivin Regulation of Beta-Cell Mass Expansion Figure 5. Expansion of beta-cell mass is impaired in RIPCre+Survivinfl/fl mice after PDL. (a) At PDL day 7, beta-cell mass expansion in the tail of pancreas in RIPcre+survivinfl/fl mice is markedly impaired compared to controls (n = 5 per genotype). (b) The increment of beta-cell number in the pancreas tail at PDL day 7 is markedly attenuated in the mutant mice compared with that in controls (n = 5 per genotype). (c) Beta-cell size is decreased in the pancreas tail of the mutant mice at PDL day 7 compared with that in sham-operated pancreas tail, but is still larger than that in PDL- treated controls (n = 5 per genotype). (d) Mutant mice exhibit increased beta-cell nucleus size in the pancreas tail both in PDL and sham-operated groups (n = 5 per genotype). (e) The increment of total islet number in pancreas tail at PDL day 7 is attenuated in the mutant mice compared to controls, mainly due to the lack of increase in the number of larger islets (n = 5 per genotype). WT, wildtype; KO, knockout. PDL, black bars; sham operation, white bars. The data represent as means 6 SE. *p,0.05, **p,0.01 vs sham operation; #P,0.05, ##p,0.01 vs control. doi:10.1371/journal.pone.0041976.g005 postnatal remodeling secondary to reduced beta-cell proliferation with perturbations in cell cycle proteins [20]. Here, we show that survivin expression increases in the islets of the ligated tail of adult mouse pancreas as early as three days post PDL, which was correlated with increased beta-cell proliferation and mass expan- sion. In contrast, RIPcre+survivinfl/fl mice with specific deletion of survivin in beta cells showed impaired beta-cell mass expansion following PDL due to defective beta-cell proliferation. PDL is a normoglycemic pancreatic injury model that stimulates beta-cell mass expansion by both beta-cell neogenesis from endogenous progenitors and self-duplication of preexisting beta cells in adult pancreas [5,22]. We found that PDL led to resurgence of survivin expression in the islets of the ligated tail of adult mouse pancreas within 2 weeks during a period of enhanced beta-cell proliferation. A recent study in mice has shown that FoxM1 is partially required for proliferation of preexisting PLoS ONE | www.plosone.org 7 August 2012 | Volume 7 | Issue 8 | e41976