A, Senescence-associated β-galactosidase activity (SA-bgal, bright blue) was detected in acini of the SDS pancreas at 30 days of age (N = 5). Sbds
P–/+ and Sbds
P–/R126T are shorthand for Sbds
CKO/+; Ptf1a
Cre/+ and Sbds
CKO/R126T; Ptf1a
Cre/+, respectively [51]. Scale bars represent 100 μm. B, 84 cellular-senescence associated genes were assayed using the SABiosciences Cellular Senescence RT2 Profiler PCR Array (QIAGEN) with total RNA isolated from pancreata of mice at 15 and 25 days of age. Table lists transcripts that showed statistically significant changes relative to control genes at at least one of the two assayed time points (see also S2 Table). Fold change: Sbds
P-/R126T/Sbds
P-/+. Criteria for significance (as per supplier’s instructions): ≥3 fold difference with a P-value of <0.05, N = 3 at each time point. C and D, Quantitative transcript analysis. In C, fold change: Sbds
P-/R126T/Sbds
P-/+; N = 4 at each time point, except at E18.5 where N = 3. Criteria for significance: ≥2 fold change, P<0.05. E18.5 pancreas expression is relative to Tbp; P8-P25 expression is relative to Gapdh. In D, fold change: Sbds
R126T/R126T/Sbds
R126T/+; N = 4. Criteria for significance: ≥2 fold change, P<0.05. Brain and liver expression is relative to Actb; bone expression is relative to Tbp. All P-values calculated using unpaired, two-tailed T-tests. Red indicates down-regulation, blue indicates up-regulation. Abbreviations in B: Akt1: Thymoma viral proto-oncogene 1; Cd44: CD44 antigen; Cdkn1a: Cyclin-dependent kinase inhibitor 1A; Ckdn2b: Cyclin-dependent kinase inhibitor 2B; Col1a1: Collagen, type I, alpha 1; Creg1: Cellular repressor of E1A-stimulated genes 1; Egr1: Early growth response 1; Ets1: E26 avian leukemia oncogene 1, 5’ domain; Fn1: Fibronectin 1; Hras1: Harvey rat sarcoma virus oncogene 1; Ifng: Interferon gamma; Igfbp5: Insulin-like growth factor binding protein 5; Igfbp7: Insulin-like growth factor binding protein 7; Interferon regulatory factor 3; Irf5: Interferon regulatory factor 5; Irf7: Interferon regulatory factor 7; Myc: Myelocytomatosis oncogene; Nfkb1: Nuclear factor of kappa light polypeptide gene enhancer in B-cells 1, p105; Sparc: Secreted acidic cysteine rich glycoprotein (osteonectin; Tbx3: T-box-3; Tgfb1: Transforming growth factor, beta 1; Tgfb1i1: Transforming growth factor beta 1 induced transcript 1.