1
Mouse
310
200 150(Ma)
100
166
120
148
050
175
148
CatDog
PigCow
Armadillo
Elephant
Dolphin120 65
2
166 Ma
148 Ma
3
= Placenta Placenta
4
Phascolarctos cinereusParameles nasta
Setonix brachurusDasyurus viverrinus
Eastern Quoll
“Reproductive physiology of marsupials” by Tyndale-Biscoe and Renfree 1987 5
10
Surani A et al. Nature 1984, McGrath J & Solter D Cell 1984, Mann J & Lovell-Badge R Nature 1984 6
7 8
117 172 1812
Peg1/Mest
Impact
Peg5/Nnat
GnasxlNesp
Nespas
Snrpn
Znf127
Ndn
IpwUbe3a
Snurf
Znf127as
Peg3 Usp29
Zim1
p57Kip2
Igf2
Ins2Mash2
H19
Peg8/Igf2as
Kvlqt1
Impt1
obph1
Msuit
Kvlqt1as/Lit1
Tapa1
Ipl
AirIgf2r
U2af1-rs1Meg1/Grb10
6
Peg9/Dlk1Meg3/Gtl2
Peg11/Rtl1antiPeg11
Meg9/Mirg Meg8/Rian
Dio3
Peg10Scge
Neurabin Pon2 Pon3
Pdk4 Asb4
Dio3as
Peg12/Frat3
Gnas
Zim3Zfp264
Ube3aas
Magel2
Tssc4
CalcrDlx5
Murr1
Slc22a3Slc22a2
9 15
Peg13Ata3
Rasgrf1A19
9 10
DMR
Peg10
Peg10
Sgce
Sgce
DMR: differentially methylated regionDMR
11
Photo at day 11.0
placenta
Peg10 (+/+)
placentaPeg10 (+/-)
Peg10 (+/+)
Peg10 (+/-)
placentayolk sac embryo
Peg10 KO
Wild type
12
13
( )
Layer I Layer II Layer III
14
15
( )
( )
( )
( )
(
( )
16
117 172 1812
Peg1/Mest
Impact
Peg5/Nnat
GnasxlNesp
Nespas
Snrpn
Znf127
Ndn
IpwUbe3a
Snurf
Znf127as
Peg3 Usp29
Zim1
p57Kip2
Igf2
Ins2Mash2
H19
Peg8/Igf2as
Kvlqt1
Impt1
obph1
Msuit
Kvlqt1as/Lit1
Tapa1
Ipl
AirIgf2r
U2af1-rs1Meg1/Grb10
6
Peg9/Dlk1Meg3/Gtl2
Peg11/Rtl1antiPeg11
Meg9/Mirg Meg8/Rian
Dio3
Peg10Scge
Neurabin Pon2 Pon3
Pdk4 Asb4
Dio3as
Peg12/Frat3
Gnas
Zim3Zfp264
Ube3aas
Magel2
Tssc4
CalcrDlx5
Murr1
Slc22a3Slc22a2
9 15
Peg13Ata3
Rasgrf1A19
17 18
19
Southern probe 1 Southern probe 2
neo DT-A
neo
Southern probe 1 Southern probe 2
: loxP site
7.3 kb 1.8 kb
B E B E
B EE
B E
B E B E
Homologous recombnation
Recombination at loxP site by Cre recombinase
B : Bgl II
E : Eco RV
splicing
antiPeg11
Peg11/Rtl1
Sekita Y et al. Nat Genet 2008 20
WT Pat-KO WT Mat-KO
Peg11/Rtl1
-actin
21
WT Peg11 Pat-KO
50%
Peg11 Pat-KO50% 16.5
WT: white bars Pat-KO: black bars ()
22
500 m 5 m10 m
la
sp
la
sp
15.5
23
400
800
1200
(μm2) Cross-section area of fetal capillariesWT Mat-KO
24
Sekita Y et al. Nat Genet 2008
Ono R et al. Nat Genet 2006
25
ERVs: endogenous retroviruses PR: , IN: , RT: )
Gag: group-specific antigenPol: RNA DNA
Env:
LTR:
26
27
CCHC
( 12F1)
Sushi-ichi retrotransposon(puffer fish: AF030881)
(6A1)
GAG: 371 a.a.DSG YLDD DAS HHCC DDEPOL: 1187 a.a.
ORF1: 376 a.a.
ORF2: 556 a.a.
(XD)CCHC
DSG
(15E2)
(XA5)
(XC3)
(XF2)
(XF2)
CCHC
DSG
DSG
(XA5)
CCHC
CCHC
1744 a.a.
243 a.a.
113 a.a.
113 a.a.
112 a.a.
151 a.a.
599 a.a.
ORF1: 553 a.a.ORF2: 145 a.a.
1494 a.a.
304 a.a.
Peg11/Rtl1/Sirh2
Peg10/Sirh1
Sirh9/Zcchc5
Sirh7/Ldoc1
Sirh8/Rgag4
Sirh10/Rgag1
Sirh11/Zcchc16
Sirh4, 5, 6
Sirh3/Ldoc1l
Mart: mammalian retrotransposon-derived (J-N Volff) Sushi: sushi-ichi retrotoranposon-derived (A Ferguson-Smith)
-ichi related retrotoranposon homologues (Sirh)
28
Sirh11/Zcchc16 Sirh1/Peg10Sirh2/Peg11
Sirh7/Ldoc1
Sirh3/Ldoc1lSirh8/Rgag4
29
SIRH
pseudoSIRH12
PEG11/SIRH2, SIRH3SIRH4-6, SIRH7, SIHR8, SIRH9, SIHR10, SIRH11
PEG10/SIRH1
SIRH12
Mammals
pseudoSIRH11
30
:SIRH family 11 : 2 PEG10 PNMA family 19 : 1
:SIRH family 11 : 2 PEG10 PNMA family 19 : 1
31
DNA“ ”
1. LTR
32