Proceedings of the National Academy of Sciences - PNAS, 2014-05, Vol.111 (20), p.7260-7265
2014
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- Autor(en) / Beteiligte
- Titel
- Engraftment of human iPS cells and allogeneic porcine cells into pigs with inactivated RAG2 and accompanying severe combined immunodeficiency
- Ist Teil von
- Proceedings of the National Academy of Sciences - PNAS, 2014-05, Vol.111 (20), p.7260-7265
- Ort / Verlag
- United States: National Academy of Sciences
- Erscheinungsjahr
- 2014
- Quelle
- Electronic Journals Library
- Beschreibungen/Notizen
- Pigs with severe combined immunodeficiency (SCID) may provide useful models for regenerative medicine, xenotransplantation, and tumor development and will aid in developing therapies for human SCID patients. Using a reporter-guided transcription activator-like effector nuclease (TALEN) system, we generated targeted modifications of recombination activating gene (RAG) 2 in somatic cells at high efficiency, including some that affected both alleles. Somatic-cell nuclear transfer performed with the mutated cells produced pigs with RAG2 mutations without integrated exogenous DNA. Biallelically modified pigs either lacked a thymus or had one that was underdeveloped. Their splenic white pulp lacked B and T cells. Under a conventional housing environment, the biallelic RAG2 mutants manifested a “failure to thrive” phenotype, with signs of inflammation and apoptosis in the spleen compared with age-matched wild-type animals by the time they were 4 wk of age. Pigs raised in a clean environment were healthier and, following injection of human induced pluripotent stem cells (iPSCs), quickly developed mature teratomas representing all three germ layers. The pigs also tolerated grafts of allogeneic porcine trophoblast stem cells. These SCID pigs should have a variety of uses in transplantation biology.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0027-8424eISSN: 1091-6490DOI: 10.1073/pnas.1406376111Titel-ID: cdi_proquest_journals_1532769332
- Format
- –
- Schlagworte
- Alleles, Animals, B lymphocytes, Base Sequence, Biological Sciences, Disease models, DNA-Binding Proteins - genetics, Fibroblasts - metabolism, Genotype, Hogs, Humans, Induced pluripotent stem cells, Induced Pluripotent Stem Cells - cytology, Induced Pluripotent Stem Cells - transplantation, Molecular Sequence Data, Mutation, Nuclear Proteins - genetics, Phenotype, Phenotypes, Regeneration, Severe Combined Immunodeficiency - genetics, Severe Combined Immunodeficiency - metabolism, Severe Combined Immunodeficiency - therapy, Somatic cells, Stem cells, Swine, Swine, Miniature, T cell receptors, T lymphocytes, Thymus Gland - metabolism, Transplantation, Heterologous, Tumors, Umbilical Cord - cytology