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1 ! ""! #$%"$!!!!!!! &'()(!*+!,-(.(/012! ')) /+123'()(/27)!
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5 ! ')) /2EF/G'5H;:(E(C+)1)(:;<E>5IE<>>;B;G<);(2/').!
6 !!!!!!!!!!!!! $!
7 ! ')) /2EF/G'5H;:(E(C+)1)(:;<E>5IE<>>;B;G<);(2/').!
8 !
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10 JKH! Viral genome Retroviral infection to germ cells Exogenous retroviruses entry Host genome Integration Ancestor Progeny ERV!
11 !!
12 L<:);2!7)!<E!M"NNNO!P/!H;:(E/!%84!#$$#Q#$$N!
13 ! &7<:>(2!R!K(':.<22!M#99#O!P/!H;:(E/!%S4!T89"QT89$!
14 ! &7<:>(2!R!K(':.<22!M#99#O!P/!H;:(E/!%S4!T89"QT89$!
15 ! U<2>72!R!U7>E(3QU<::;>(2!M#99$O!VDF<2G7>!;2!W()<2;G<E!K7>7<:G' $"4"ST"N8/!
16 ! 89! $! $!!
17
18 360my 230my icems
19 icems
20 ph5.5 SG1 SG2 SG3 ph7.5 Tight Junction Furuse and Tsukita et al., JCB 156: , 2002 Langerhans Cell Network Reviewed by Kubo, Nagao and Amagai, JCI 122: , 2012 icems
21 SG1 SASPase Human Mouse aa Protease TM 82% identity aa Protease TM? Human SASPase: Bernard et al., J. Invest. Dermatol Mouse SASPase: Matsui et al., J. Biol. Chem Mouse Taps: Rhiemeier et al., Am. J. Pathol (34kDa) (32kDa) SG1 +/- -/- Mouse Back Skin Epidermis SG1 icems Matsui et al., EMBO Mol. Med. 2011
22 ProfilaggrinSASPase SASP +/+ SASP -/- Cit Cit Cit? Keratin Filaggrin SASP SASP SASP SASP Profilaggrin Matsui et al., EMBO Mol. Med icems
23 360my 230my? icems
24 1 SASPase 2SASPase ( ) 3SASPase SASPase
25 ! Uterine ')) G/D;>G(F7:+'(>3;)<E/G(.572G+GE(37D;<5;.CX').5Y0ZQ#A/').!!!!
26 W<?7:!7)!<E/[!K73:(D1G);(2!M#99NO!"8A4!"NTQ#9N!
27 Nature(2000) 403: Syncytin is a captive retroviral envelope protein involved in human placental morphogenesis SHA MI, XINHUA LEE, XIANG-PING LI, GEERTRUIDA M. VELDMAN, HEATHER FINNERTY, LISA RACIE, EDWARD LAVALLIE, XIANG-YANG TANG, PHILIPPE EDOUARD, STEVE HOWES, JAMES C. KEITH JR & JOHN M. MCCOY* Genetics Institute, Inc., 87 CambridgePark Drive, Cambridge, Massachusetts 02140, USA * Present address: Biogen Inc., 14 Cambridge Center, Cambridge, Massachusetts 02142, USA
28 Nature(2000) 403:
29 Nature(2000) 403:
30 !!!!! %9!!A9\!!
31 !! Binucleate cells Mononucleate cells!!
32 !!
33 !!
34 !!
35 W(F;27!72D(C72(1>!:7):(F;:1>!]WJKHQ]! BERV-K1 BERV-K2 ^-K! gag pol %&'$ ^-K! ^-K! gag!"#$ %&'$ ^-K! pro pro SP SU TM SP SU TM -2 Hydrophobicity Hydrophobicity Amino acid sequence Amino acid sequence env2erv W<*<!7)!<E/!M#9""O!AT4"#8%Q"#$T!
36 J2F! beta BERV-K1 BERV-K2 enjsrv delta alpha gamma lenti BERV-Ks W<*<!7)!<E/!M#9""O!AT4"#8%Q"#$T!
37 WJKHQ]!%&'!.KZV>! BERV-K1 BERV-K relative expression levels (BERV-K1/GAPDH) Pl Lu Li Sp He Mu Ki Sk Te EM relative expression levels (BERV-K2/GAPDH) Pl Lu Li Sp He Mu Ki Sk Te EM W<*<!7)!<E/!M#9""O!AT4"#8%Q"#$T!
38 WJKHQ]!%&'$ %&'$ 3_YT5W]J2F`^VY^-K! ^-K! (kda) Empty K1 K2 &:7G1:>(:! _&! cleavage _a! TM Cos-7 cells cleavage FLAG !!!!!!!!!!!!!!!!!!!!!!!!!!!-L! -FLAG -Tubulin Env TM EnvK1
39 WJKHQ]!J2F! Env Fusion Cos7/GFP/Env Cos7/DsRed Empty BERV-K1 BERV-K2 VSV-G BERV-K1 Env
40 WJKHQ]!J2F! Fusion ^1G! Cos-7/Env (effector cells) Relative luciferase activities Cos-7 cells Target cells Empty K1 K2 VSV-G Relative luciferase activities ^1G! Bovine endometrial cells Empty K1 K2 VSV-G BERV-K1 Env
41 ! BERV-K1 Env BERV-K1 Env
42 WJKHQ]"!
43 !
44 ! WJKHQ]"! (%)*+$ (%)**,-.#*$ /0&10.2&34$ /0&10.2&35$ _+2G+);2!"! _+2G+);2!#!!
45 !!
46 8! UbHQ"! UbHQ#! _bh VYL! bbb! H;>2<! `bh! KJ^b]! JbVH!!!! UJKHQ^! cd_h! U`H! ``H! K_H! LL-H! L&LH! P_KH!! bb! cjuhq"! cjuhq#! W^H!!! UJKHQK! L1^H! `7^H! Y<^H! UJKHQc! &JKH! ](KH! U-^HQ#! U-^HQ"!! b!
47 !! SINE T[999! LINE 30
48 !! ](KH! "#$! YV^H! "#$! 678$19:"#2!JKH!!!!!!! "#$! "#$!!
49 d76<22;7e!7)!<e/!h;:<e!_<b7)+!r!je):<27(1>!vc72)>!-7>);2c!b(:!h7)7:;2<:+!h<gg;27>!m#9"9o!!!!
50 ! Q"[!8!Y-!]f!3;C! &JKH!
51 Vaccines A B C D E F G H I RT-PCR (env) d;:7g)! Real time RT-PCR (Copy number/ml) 4.5 x x x10 6 BGL BGL 1.0 x10 6 BGL 2.1 x x10 8 LacZ MR assay f2!g7ee>! PCR TCID 50 (/shot) 1,800 1, ND** ND ND ND 10,000! 180 *BGL: Background level; **ND: not detected; ***NT: not tested L;+<?<6<!7)!<E/!;$<2:"#=!M#9"9O[!0(>';@<6<!7)!<E/!52"#")219#8!M#9"#O!!
52 KdQ""$ KdQ""$!F;:1>!;2B7G)>!D(C>! PCR (env) "T9 #9"9O!
53 ! gg!
54 !
55 ! #!!!!., Vol. 26, pp (2010).
56 !!! MIK&O!! $!M_;.;<2!:7):(F;:1>!)+37!$4!_KH$O!!
57
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59 !!MO!
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61 ! _KH$!!!! _KH$!! _KH$!
62 !! _KH!!
63 KdQ""$hM`GJHi_KHO#! )9)3!"#! %&'! L^H! _KH! _KH!!!! KdQ""$!
64 !!!!!j!!! j!!!!!!!!!!!!!!!
65 !!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!
66 ! 3 2 1! )<@<F7)kC((/=3!
67 ! #9"#%"#!
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