دورية أكاديمية
أعرض في EDS

Strong xenoprotective function by single-copy transgenes placed sequentially at a permissive locus.

التفاصيل البيبلوغرافية
العنوان: Strong xenoprotective function by single-copy transgenes placed sequentially at a permissive locus.
المؤلفون: Rieblinger B; Chair of Livestock Biotechnology, School of Life Sciences Weihenstephan, Technische Universität München, Freising, Germany., Fischer K; Chair of Livestock Biotechnology, School of Life Sciences Weihenstephan, Technische Universität München, Freising, Germany., Kind A; Chair of Livestock Biotechnology, School of Life Sciences Weihenstephan, Technische Universität München, Freising, Germany., Saller BS; Chair of Livestock Biotechnology, School of Life Sciences Weihenstephan, Technische Universität München, Freising, Germany., Baars W; Transplant Laboratory, Department for General-, Visceral- and Transplantation Surgery, Hannover Medical School, Hannover, Germany., Schuster M; Medizinische Klinik and Polyklinik IV, Diabetes Zentrum, Klinikum der Ludwig-Maximilians-Universität München, Munich, Germany., Wolf-van Buerck L; Medizinische Klinik and Polyklinik IV, Diabetes Zentrum, Klinikum der Ludwig-Maximilians-Universität München, Munich, Germany., Schäffler A; Chair of Livestock Biotechnology, School of Life Sciences Weihenstephan, Technische Universität München, Freising, Germany., Flisikowska T; Chair of Livestock Biotechnology, School of Life Sciences Weihenstephan, Technische Universität München, Freising, Germany., Kurome M; Chair of Molecular Animal Breeding and Biotechnology, Ludwig-Maximilians-Universität München, Oberschleissheim, Germany., Zakhartchenko V; Chair of Molecular Animal Breeding and Biotechnology, Ludwig-Maximilians-Universität München, Oberschleissheim, Germany., Kessler B; Chair of Molecular Animal Breeding and Biotechnology, Ludwig-Maximilians-Universität München, Oberschleissheim, Germany., Flisikowski K; Chair of Livestock Biotechnology, School of Life Sciences Weihenstephan, Technische Universität München, Freising, Germany., Wolf E; Chair of Molecular Animal Breeding and Biotechnology, Ludwig-Maximilians-Universität München, Oberschleissheim, Germany., Seissler J; Medizinische Klinik and Polyklinik IV, Diabetes Zentrum, Klinikum der Ludwig-Maximilians-Universität München, Munich, Germany., Schwinzer R; Transplant Laboratory, Department for General-, Visceral- and Transplantation Surgery, Hannover Medical School, Hannover, Germany., Schnieke A; Chair of Livestock Biotechnology, School of Life Sciences Weihenstephan, Technische Universität München, Freising, Germany.
المصدر: Xenotransplantation [Xenotransplantation] 2018 Mar; Vol. 25 (2), pp. e12382. Date of Electronic Publication: 2018 Jan 23.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Munksgaard International Publishers Country of Publication: Denmark NLM ID: 9438793 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1399-3089 (Electronic) Linking ISSN: 0908665X NLM ISO Abbreviation: Xenotransplantation Subsets: MEDLINE
أسماء مطبوعة: Publication: Copenhagen : Munksgaard International Publishers
Original Publication: Copenhagen : Munksgaard, c1994-
مواضيع طبية MeSH: Transplantation, Heterologous*/methods, Insulin-Secreting Cells/*cytology, Animals ; Animals, Genetically Modified/genetics ; CD55 Antigens/genetics ; CD59 Antigens/genetics ; Fibroblasts/cytology ; Genetic Loci ; Heme Oxygenase-1/genetics ; Humans ; Promoter Regions, Genetic/genetics ; Swine ; Transgenes/genetics
مستخلص: Background: Multiple xenoprotective transgenes are best grouped at a single locus to avoid segregation during breeding and simplify production of donor animals.
Methods: We used transgene stacking to place a human CD55 transgene adjacent to a human heme oxygenase 1 construct at the porcine ROSA26 locus. A transgenic pig was analyzed by PCR, RT-PCR, droplet digital PCR, immunohistochemistry, immunofluorescence, and flow cytometry. Resistance to complement-mediated cell lysis and caspase 3/7 activation were determined in vitro.
Results: The ROSA26 locus was retargeted efficiently, and animals were generated by nuclear transfer. RNA and protein analyses revealed abundant expression in all organs analyzed, including pancreatic beta cells. Transgenic porcine kidney fibroblasts were almost completely protected against complement-mediated lysis and showed reduced caspase 3/7 activation.
Conclusion: Step-by-step placement enables highly expressed single-copy xenoprotective transgenes to be grouped at porcine ROSA26.
(© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)
فهرسة مساهمة: Keywords: ROSA26; CD55; heme oxygenase 1; transgene stacking; xenotransplantation
المشرفين على المادة: 0 (CD55 Antigens)
0 (CD59 Antigens)
EC 1.14.14.18 (Heme Oxygenase-1)
تواريخ الأحداث: Date Created: 20180124 Date Completed: 20180928 Latest Revision: 20181001
رمز التحديث: 20221213
DOI: 10.1111/xen.12382
PMID: 29359453
قاعدة البيانات: MEDLINE
الوصف
تدمد:1399-3089
DOI:10.1111/xen.12382