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      Production and Breeding of Transgenic Cloned Pigs Expressing Human CD73

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      https://www.riss.kr/link?id=A105113744

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      다국어 초록 (Multilingual Abstract)

      One of the reasons to causing blood coagulation in the tissue of xenografted organs was known to incompati-bility of the blood coagulation and anti-coagulation regulatory system between TG pigs and primates. Thus, overexpression of human CD73 (hCD73) ...

      One of the reasons to causing blood coagulation in the tissue of xenografted organs was known to incompati-bility of the blood coagulation and anti-coagulation regulatory system between TG pigs and primates. Thus, overexpression of human CD73 (hCD73) in the pig endothelial cells is considered as a method to reduce coagulopathy after pig-to-non-human-primate xenotransplantation. This study was performed to produce and breed transgenic pigs expressing hCD73 for the studies immune rejection responses and could provide a successful application of xenotransplantation. The transgenic cells were con-structed an hCD73 expression vector under control porcine Icam2 promoter (pIcam2-hCD73) and established donor cell lines expressing hCD73. The numbers of transferred reconstructed embryos were 127 ± 18.9. The pregnancy and delivery rate of surrogates were 8/18 (44%) and 3/18 (16%). The total number of delivered cloned pigs were 10 (2 alive, 7 mummy, and 1 died after birth). Among them, three live hCD73-pigs were successfully delivered by Caesarean section, but one was dead af-ter birth. The two hCD73 TG cloned pigs had normal reproductive ability. They mated with wild type (WT) MGH (Massachu-setts General Hospital) female sows and produced totally 16 piglets. Among them, 5 piglets were identified as hCD73 TG pigs. In conclusion, we successfully generated the hCD73 transgenic cloned pigs and produced their litters by natural mating. It can be possible to use a mate for the production of multiple transgenic pigs such as α-1,3-galactosyltransferase knock-out /hCD46 for xenotransplantation.

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      참고문헌 (Reference)

      1 오건봉, "돼지 혈관내피세포 특이적 CD73 발현 벡터가 도입된 돼지 섬유아세포생산" 한국수정란이식학회 31 (31): 161-168, 2016

      2 Tseng YL, "alpha 1,3-Galactosyltransferase gene-knockout pig heart trans-plantation in baboons with survival approaching 6 months" 80 : 1493-1500, 2005

      3 Wheeler DG, "Transgenic swine: expression of human CD39 protects against myocardial injury" 52 : 958-961, 2012

      4 Shimizu A, "Thrombotic microangiopathy associated with humoral rejection of cardiac xenografts from alpha1,3-galactosyltransferase gene-knockout pigs in baboons" 172 : 1471-1481, 2008

      5 Houser SL, "Thrombotic microangiopathy and graft arteriopathy in pig hearts following transplantation into baboons" 11 : 416-425, 2004

      6 Lin CC, "Recipient tissue factor expres-sion is associated with consumptive coagulopathy in pig-to-primate kidney xenotransplantation" 10 : 1556-1568, 2010

      7 Arulkumaran N, "Purinergic signaling in inflammato-ry renal disease" 4 : 1-7, 2013

      8 Nottle MB, "Production of homozygous alpha-1,3-galactosyltransferase knockout pigs by breeding and somatic cell nuclear transfer" 14 : 339-344, 2007

      9 Choi K, "Production of heterozygous alpha 1,3-galactosyltransferase (GGTA1) knock-out transgenic miniature pigs expressing human CD39" 26 : 209-224, 2017

      10 Kolber-Simonds D, "Production of alpha-1,3-galactosyl-transferase null pigs by means of nuclear transfer with fibroblasts bearing loss of heterozygosity mutations" 101 : 7335-7340, 2004

      1 오건봉, "돼지 혈관내피세포 특이적 CD73 발현 벡터가 도입된 돼지 섬유아세포생산" 한국수정란이식학회 31 (31): 161-168, 2016

      2 Tseng YL, "alpha 1,3-Galactosyltransferase gene-knockout pig heart trans-plantation in baboons with survival approaching 6 months" 80 : 1493-1500, 2005

      3 Wheeler DG, "Transgenic swine: expression of human CD39 protects against myocardial injury" 52 : 958-961, 2012

      4 Shimizu A, "Thrombotic microangiopathy associated with humoral rejection of cardiac xenografts from alpha1,3-galactosyltransferase gene-knockout pigs in baboons" 172 : 1471-1481, 2008

      5 Houser SL, "Thrombotic microangiopathy and graft arteriopathy in pig hearts following transplantation into baboons" 11 : 416-425, 2004

      6 Lin CC, "Recipient tissue factor expres-sion is associated with consumptive coagulopathy in pig-to-primate kidney xenotransplantation" 10 : 1556-1568, 2010

      7 Arulkumaran N, "Purinergic signaling in inflammato-ry renal disease" 4 : 1-7, 2013

      8 Nottle MB, "Production of homozygous alpha-1,3-galactosyltransferase knockout pigs by breeding and somatic cell nuclear transfer" 14 : 339-344, 2007

      9 Choi K, "Production of heterozygous alpha 1,3-galactosyltransferase (GGTA1) knock-out transgenic miniature pigs expressing human CD39" 26 : 209-224, 2017

      10 Kolber-Simonds D, "Production of alpha-1,3-galactosyl-transferase null pigs by means of nuclear transfer with fibroblasts bearing loss of heterozygosity mutations" 101 : 7335-7340, 2004

      11 Fujimura T, "Production of alpha 1,3-galactosyltransferase gene-deficient pigs by somatic cell nuclear transfer: a novel selection method for gal alpha 1,3-Gal antigen-deficient cells" 75 : 1372-1378, 2008

      12 황인설, "Production of Cloned Korean Native Pig by Somatic Cell Nuclear Transfer" 한국발생생물학회 19 (19): 79-84, 2015

      13 Phelps CJ, "Produc-tion of alpha 1,3-galactosyltransferase-deficient pigs" 299 : 411-414, 2003

      14 Zhang B, "Platelet aggregation and thrombosis in xenotransplantation between pigs and humans" 121 : 433-441, 2008

      15 Iwase H, "Pig kidney graft survival in a baboon for 136 days: longest lifesupporting organ graft survival to date" 22 : 302-309, 2015

      16 Sitkovsky MV, "Physiological control of immune response and inflammatory tissue damage by hypoxia-inducible factors and adenosine A2A receptors" 22 : 657-682, 2004

      17 Daval JL, "Physiological and pharmacological properties of adenosine: therapeutic implications" 49 : 1435-1453, 1991

      18 Kim H, "Outcomes of alpha 1,3-GT-knockout porcine heart transplants into a preclinical nonhuman primate model" 45 : 3085-3091, 2013

      19 Khalpey Z, "Loss of ecto-50 nucleotidase from porcine en-dothelial cells after exposure to human blood: implica-tions for xenotransplantation" 1741 : 191-198, 2005

      20 Higginbotham L, "Long-term survival of pig-to-primate renal xenotransplant using costimulation-blockade immuno-suppression" s72-s73, 2015

      21 Crikis S, "Intravascular throm-bosis in discordant xenotransplantation" 82 : 1119-1123, 2006

      22 Kuwaki K, "Heart transplantation in baboons using alpha 1, 3-galactosyltransferase gene-knockout pigs as donors: initial experience" 11 : 29-31, 2005

      23 Kwon DJ, "Generation of α-1,3-galactosyltransferase knocked-out transgenic cloned pigs with knocked-in five human genes" 26 : 153-163, 2017

      24 Zimmermann H, "Extracellular purine metabolism" 39 : 337-352, 1996

      25 Delikouras A, "Endothelial cell cytoprotection in-duced in vitro by allo- or xenoreactive antibodies is mediated by signaling through adenosine A2 receptors" 33 : 3127-3135, 2003

      26 Rocha PN, "Effector mechanisms in transplant rejection" 196 : 51-64, 2003

      27 Lambrigts D, "Discordant organ xenotransplantation in primates: world experi-ence and current status" 66 : 547-561, 1998

      28 Cowan PJ, "Complement activation and coagulation in xenotransplantation" 87 : 203-208, 2009

      29 Lin CC, "Coagulation dysre-gulation as a barrier to xenotransplantation in the pri-mate" 21 : 75-80, 2009

      30 Cowan PJ, "Coagulation and the xenograft endothe-lium" 14 : 7-12, 2007

      31 Cooper DK, "Clinical lung xeno-transplantation-- what donor genetic modifications may be necessary?" 19 : 144-158, 2012

      32 Ekser B, "Clin-ical xenotransplantation: the next medical revolution?" 379 : 672-683, 2012

      33 Mohiuddin MM, "Chimeric 2C10R4 anti-CD40 antibody therapy is critical for long-term survival of GTKO.hCD46.hTBM pig-to-primate cardi-ac xenograft" 7 : 1-10, 2016

      34 Lee HJ, "Characterization of transgenic pigs that express human decay accelerating factor and cell membrane-tethered human tissue factor pathway inhibitor" 46 : 325-332, 2011

      35 McGregor CG, "Cardiac xenotransplantation: progress toward the clinic" 78 : 1569-1575, 2004

      36 Li P, "Biallelic knockout of the alpha-1,3 galactosyltransferase gene in porcine liver-derived cells using zinc finger nucleases" 181 : e39-e45, 2013

      37 Bauerle JD, "Adenosine generation and signaling during acute kid-ney injury" 22 : 14-20, 2011

      38 Chen G, "Acute rejection is asso-ciated with antibodies to non-Gal antigens in baboons using Gal-knockout pig kidneys" 11 : 1295-1298, 2005

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      학술지 이력

      학술지 이력
      연월일 이력구분 이력상세 등재구분
      2027 평가예정 재인증평가 신청대상 (재인증)
      2021-01-01 평가 등재학술지 유지 (재인증) KCI등재
      2018-01-01 평가 등재학술지 유지 (등재유지) KCI등재
      2015-01-01 평가 등재학술지 유지 (등재유지) KCI등재
      2011-01-01 평가 등재학술지 선정 (등재후보2차) KCI등재
      2010-01-01 평가 등재후보 1차 PASS (등재후보1차) KCI등재후보
      2009-01-01 평가 등재후보학술지 유지 (등재후보2차) KCI등재후보
      2008-01-01 평가 등재후보 1차 PASS (등재후보1차) KCI등재후보
      2007-01-01 평가 등재후보학술지 유지 (등재후보1차) KCI등재후보
      2005-01-01 평가 등재후보학술지 선정 (신규평가) KCI등재후보
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      학술지 인용정보

      학술지 인용정보
      기준연도 WOS-KCI 통합IF(2년) KCIF(2년) KCIF(3년)
      2016 0.4 0.4 0.32
      KCIF(4년) KCIF(5년) 중심성지수(3년) 즉시성지수
      0.27 0.25 0.394 0.13
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