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