title: Ubiquitous LEA29Y Expression Blocks T Cell Co-Stimulation but Permits Sexual Reproduction in Genetically Modified Pigs.
abstract: We have successfully established and characterized a genetically modified pig line with ubiquitous expression of LEA29Y, a human CTLA4-Ig derivate. LEA29Y binds human B7.1/CD80 and B7.2/CD86 with high affinity and is thus a potent inhibitor of T cell co-stimulation via this pathway. We have characterized the expression pattern and the biological function of the transgene as well as its impact on the porcine immune system and have evaluated the potential of these transgenic pigs to propagate via assisted breeding methods. The analysis of LEA29Y expression in serum and multiple organs of CAG-LEA transgenic pigs revealed that these animals produce a biologically active transgenic product at a considerable level. They present with an immune system affected by transgene expression, but can be maintained until sexual maturity and propagated by assisted reproduction techniques. Based on previous experience with pancreatic islets expressing LEA29Y, tissues from CAG-LEA29Y transgenic pigs should be protected against rejection by human T cells. Furthermore, their immune-compromised phenotype makes CAG-LEA29Y transgenic pigs an interesting large animal model for testing human cell therapies and will provide an important tool for further clarifying the LEA29Y mode of action.
authors.affiliation: Chair for Molecular Animal Breeding and Biotechnology, Gene Center and Department of Veterinary Sciences, LMU Munich, Munich, Germany.
authors.forename: Andrea
authors.initials: A
authors.lastname: Bähr
authors.affiliation: Institute of Immunology, Department of Pathobiology, University of Veterinary Medicine, Vienna, Austria.
authors.forename: Tobias
authors.initials: T
authors.lastname: Käser
authors.affiliation: Chair for Molecular Animal Breeding and Biotechnology, Gene Center and Department of Veterinary Sciences, LMU Munich, Munich, Germany.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Kemter
authors.affiliation: Institute of Immunology, Department of Pathobiology, University of Veterinary Medicine, Vienna, Austria.
authors.forename: Wilhelm
authors.initials: W
authors.lastname: Gerner
authors.affiliation: Chair for Molecular Animal Breeding and Biotechnology, Gene Center and Department of Veterinary Sciences, LMU Munich, Munich, Germany.
authors.forename: Mayuko
authors.initials: M
authors.lastname: Kurome
authors.affiliation: Transplant Laboratory, Medizinische Hochschule Hannover, Hannover, Germany.
authors.forename: Wiebke
authors.initials: W
authors.lastname: Baars
authors.affiliation: Institute of Veterinary Pathology, Center for Clinical Veterinary Medicine, LMU Munich, Munich, Germany.
authors.forename: Nadja
authors.initials: N
authors.lastname: Herbach
authors.affiliation: Institute of Anatomy, Histology and Embryology, Department of Pathobiology, University of Veterinary Medicine, Vienna, Austria.
authors.forename: Kirsti
authors.initials: K
authors.lastname: Witter
authors.affiliation: Chair for Molecular Animal Breeding and Biotechnology, Gene Center and Department of Veterinary Sciences, LMU Munich, Munich, Germany.
authors.forename: Annegret
authors.initials: A
authors.lastname: Wünsch
authors.affiliation: Institute of Immunology, Department of Pathobiology, University of Veterinary Medicine, Vienna, Austria.
authors.forename: Stephanie C
authors.initials: SC
authors.lastname: Talker
authors.affiliation: Chair for Molecular Animal Breeding and Biotechnology, Gene Center and Department of Veterinary Sciences, LMU Munich, Munich, Germany.
authors.forename: Barbara
authors.initials: B
authors.lastname: Kessler
authors.affiliation: Meiji University International Institute for Bio-Resource Research, Kawasaki, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nagashima
authors.affiliation: Institute of Immunology, Department of Pathobiology, University of Veterinary Medicine, Vienna, Austria.
authors.forename: Armin
authors.initials: A
authors.lastname: Saalmüller
authors.affiliation: Transplant Laboratory, Medizinische Hochschule Hannover, Hannover, Germany.
authors.forename: Reinhard
authors.initials: R
authors.lastname: Schwinzer
authors.affiliation: Chair for Molecular Animal Breeding and Biotechnology, Gene Center and Department of Veterinary Sciences, LMU Munich, Munich, Germany.
authors.forename: Eckhard
authors.initials: E
authors.lastname: Wolf
authors.affiliation: Chair for Molecular Animal Breeding and Biotechnology, Gene Center and Department of Veterinary Sciences, LMU Munich, Munich, Germany.
authors.forename: Nikolai
authors.initials: N
authors.lastname: Klymiuk
mesh_terms: D000069594:Abatacept / Q000378:metabolism*; D000818:Animals; D030801:Animals, Genetically Modified; D000938:Antigen-Presenting Cells / Q000378:metabolism; D019976:Cloning, Organism; D017124:Conserved Sequence; D003433:Crosses, Genetic; D005260:Female; D005307:Fertilization in Vitro; D006801:Humans; D008198:Lymph Nodes / Q000473:pathology; D008213:Lymphocyte Activation / Q000276:immunology*; D008297:Male; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D012098:Reproduction / Q000235:genetics*; D034421:Sus scrofa / Q000235:genetics* / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D000069594:Abatacept