Cycle p19 ARF expression in pancreatic compartment (old mice) Islets Exocrine Krishnamurthy et al.,...
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Transcript of Cycle p19 ARF expression in pancreatic compartment (old mice) Islets Exocrine Krishnamurthy et al.,...
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