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Cycle

Age-induced increase in p16 INK4a expression in purified islets. p19 ARF expression in pancreatic compartment (old mice). pdx expression in pancreatic compartment (old mice). Islets. Islets. Exocrine. Old. ∆ Reaction. Exocrine. Young. Cycle. Cycle. Cycle. p16 INK4a. Arf. Pdx1. a.

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Cycle

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  1. Age-induced increase in p16INK4a expression in purified islets p19ARF expression in pancreatic compartment (old mice) pdx expression in pancreatic compartment (old mice) Islets Islets Exocrine Old ∆ Reaction Exocrine Young Cycle Cycle Cycle p16INK4a Arf Pdx1 a b c Old Islet (64-80 weeks) = 16 16 Young Islet (12-14 weeks) 8 8 4 4 2 2 1 1 Relative Expression Relative Expression 0.5 0.5 p15INK4b p18INK4c p19INK4d p21CIP p27KIP 0.25 0.25 0.13 0.13 0.06 0.06 Exocrine Islet Exocrine Islet Age: 12-14 weeks 64-80 weeks Krishnamurthy et al., Supp. Figure 1

  2. a R1 R1 1a 2 3 1b Adrenal Lung Heart Pancreas Intestine Skin Kidney Spleen Liver Geometric Mean < = undetectable in wild-type Ink4a/Arf locus PI = Intron encoded nuclease PI-SceI RI = Eco RI IIII = Variable microsatellite region  = PCR screening primers PI R1 R1 PI 1a 2 3  Linearised BAC  probe 9.8 kb 54 kb b c 32 < 16 Tg Line Lo Tg Line Hi 129SvEv C57/bl6 129SvEv 8 Relative Expression (transgenic/wild-type) 8.5 kb < 4 < 7.2 kb 2 < < < < 1 0.5 p16INK4a Arf Krishnamurthy et al., Supp. Figure 2

  3. p16INK4a +/+ p16INK4a TG lung lung cerebellum cerebellum spleen uterus pancreas spleen uterus pancreas Ink4a -/- p16INK4a IP: p16 Krishnamurthy et al., Supp. Figure 3

  4. 40 30 p16INK4a +/+ p16INK4a -/- Weight (grams) 20 10 Age: 17-20 Week 40-52 Week a b 40-52 week old mice (excluding tumor-bearing outliers) 17-20 week old mice 40-52 week old mice (all) 500 500 500 p16INK4a +/+ (N=13) p16INK4a +/+(N=10) p16INK4a +/+(N=10) p16INK4a -/- (N=13) 400 400 400 p16INK4a -/- (N=6) p16INK4a -/-(N=8) 300 Serum glucose (mg/dl) 300 300 200 200 200 100 100 100 0 20 40 60 80 100 0 20 40 60 80 100 0 20 40 60 80 100 Minutes post-IP glucose Krishnamurthy et al., Supp. Figure 4

  5. * Islet Size %Ki67+ islet cells * * Islet area (arbitrary units) ki67 positive * # 12% 10.0 10% Days post-STZ treatment 7.5 8% 5.0 6% 4% 2.5 2% 0 0% 0 4 8 12 16 20 24 28 a b 3 days post-STZ Untreated Krishnamurthy et al., Supp. Figure 5

  6. tonsil appendix Ki67 = brown stain Krishnamurthy et al., Supp. Figure 6

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