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Cycle
p19ARF expression in pancreatic compartment (old mice)
Islets
Exocrine
Krishnamurthy et al., Supp. Figure 1
a
Cycle
∆ R
ea
ctio
nAge-induced increase in p16INK4a
expression in purified islets
Old
Young
b cOld Islet (64-80 weeks)
Young Islet (12-14 weeks) =
p15INK4b p18INK4c p19INK4d p21CIP p27KIP
0.060.130.25
0.51248
16
Re
lativ
e E
xpre
ssio
n
p16INK4a
Arf
Pdx1
Exocrine Islet Exocrine Islet
12-14 weeks 64-80 weeks Age:
0.060.130.25
0.51248
16
Re
lativ
e E
xpre
ssio
npdx expression in pancreatic
compartment (old mice)
Cycle
Islets
Exocrine
Krishnamurthy et al., Supp. Figure 2
Tg
Lin
e H
i
Tg
Lin
e L
o
12
9S
vEv
C5
7/b
l6
12
9S
vEv
7.2 kb
8.5 kb
PI = Intron encoded nuclease PI-SceI
RI = Eco RIIIII = Variable microsatellite
region = PCR screening primers
R1 1 2 3R11Ink4a/Arf locus
Linearised
BAC
PI
probe
R1 1 2 3R1
9.8 kb 54 kb
PI
Re
lativ
e
Exp
ress
ion
(tr
an
sge
nic
/wild
-typ
e)
a
b c
0.5
1
2
4
8
16
32
p16INK4aArf
< < < <
<
<
<
Adrenal
Heart
IntestineKidneyLiver
Lung
Pancreas
SkinSpleen
GeometricMean
< = undetectable in wild-type
Krishnamurthy et al., Supp. Figure 3
sple
en
uter
us
panc
reas
Ink4
a -/
-
cere
bellu
m
sple
en
uter
us
panc
reas
cere
bellu
m
lung
lung
p16INK4a +/+ p16INK4a TG
p16INK4a
IP: p
16
40-52 week old mice (all)40-52 week old mice (excluding
tumor-bearing outliers)17-20 week old mice
p16INK4a +/+ (N=13)
100
200
300
400
500
0 20 40 60 80 100
p16INK4a -/- (N=13)
Se
rum
glu
co
se
(m
g/d
l)
100
200
300
400
500
0 20 40 60 80 100
p16INK4a +/+ (N=10)
p16INK4a -/- (N=8)
Minutes post-IP glucose
100
200
300
400
500
0 20 40 60 80 100
p16INK4a +/+ (N=10)p16INK4a -/- (N=6)
Krishnamurthy et al., Supp. Figure 4
17-20 Week 40-52 WeekAge:W
eig
ht
(gra
ms)
10
20
30
40 p16INK4a +/+
p16INK4a -/-
a
b
Untreated 3 days post-STZ
0
2.5
5.0
7.5
10.0
0%
2%
4%
6%
8%
10%
12%
0 4 8 12 16 20 24 28ki6
7 p
ositive
Isle
t a
rea
(a
rbitr
ary
un
its)
Days post-STZ treatment
#
*
*
*
*
Islet Size
%Ki67+ islet cells
Krishnamurthy et al., Supp. Figure 5
b
a
tonsil appendix
Krishnamurthy et al., Supp. Figure 6
Ki67 = brown stain
