Production of biallelic CMP-Neu5Ac hydroxylase knock-out pigs
| Autor: | Kiho Lee, Jeffrey J. Whyte, Clifton N. Murphy, Man-Jong Kang, Alana N. Brown, Deug-Nam Kwon, Melissa Samuel, Kwang-Wook Park, Yun-Jung Choi, Jin-Hoi Kim, Randall S. Prather, Chankyu Park, Jiude Mao, Jae-Hwan Kim |
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| Rok vydání: | 2013 |
| Předmět: |
Male
DNA End-Joining Repair Swine Xenotransplantation medicine.medical_treatment Genetic Vectors Karyotype Molecular Sequence Data Gene Expression Biology Polymorphism Single Nucleotide Article Mixed Function Oxygenases Animals Genetically Modified Gene Knockout Techniques Antigen Gene Order medicine Animals Amino Acid Sequence Homologous Recombination Zinc finger Binding Sites Multidisciplinary Base Sequence Homozygote Gene targeting Zinc Fingers Fibroblasts Molecular biology Zinc finger nuclease Genetically modified organism Phenotype Genetic Loci Gene Targeting Female Exogenous DNA Protein Binding |
| Zdroj: | Scientific Reports |
| ISSN: | 2045-2322 |
| DOI: | 10.1038/srep01981 |
| Popis: | After the knock-out (KO) of α1,3 galactosyltransfease (Gal-T), the Hanganutziu-Deicher antigen became a major antigen of the "non-Gal antigen" that is implicated in subsequent xenograft rejection. For deletion of non-Gal antigen, we successfully produced zinc finger nuclease (ZFN)-mediated monoallelic/biallelic male and female CMP-N-acetylneuraminic acid hydroxylase (CMAH) KO miniature pigs: the efficiency of the gene targeting (41.7%) was higher when donor DNA was used with the ZFN than those of ZFN alone (9.1%). Monoallelic KO pigs had no integration of exogenous DNA into their genome, indicating that this technique would provide a new avenue to reduce the risk of antibiotics resistance when organs from genetically modified pigs are transplanted into patients. Until now, both monoallelic and biallelic CMAH KO pigs are healthy and show no sign of abnormality and off-target mutations. Therefore, these CMAH null pigs on the Gal-T KO background could serve as an important model for the xenotransplantation. |
| Databáze: | OpenAIRE |
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