title: Production of biallelic CMP-Neu5Ac hydroxylase knock-out pigs.
abstract: 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.
authors.affiliation: Department of Animal Biotechnology, Konkuk University, Seoul 143-701, Republic of Korea.
authors.forename: Deug-Nam
authors.initials: DN
authors.lastname: Kwon
authors.forename: Kiho
authors.initials: K
authors.lastname: Lee
authors.forename: Man-Jong
authors.initials: MJ
authors.lastname: Kang
authors.forename: Yun-Jung
authors.initials: YJ
authors.lastname: Choi
authors.forename: Chankyu
authors.initials: C
authors.lastname: Park
authors.forename: Jeffrey J
authors.initials: JJ
authors.lastname: Whyte
authors.forename: Alana N
authors.initials: AN
authors.lastname: Brown
authors.forename: Jae-Hwan
authors.initials: JH
authors.lastname: Kim
authors.forename: Melissa
authors.initials: M
authors.lastname: Samuel
authors.forename: Jiude
authors.initials: J
authors.lastname: Mao
authors.forename: Kwang-Wook
authors.initials: KW
authors.lastname: Park
authors.forename: Clifton N
authors.initials: CN
authors.lastname: Murphy
authors.forename: Randall S
authors.initials: RS
authors.lastname: Prather
authors.forename: Jin-Hoi
authors.initials: JH
authors.lastname: Kim
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D030801:Animals, Genetically Modified; D001483:Base Sequence; D001665:Binding Sites; D059766:DNA End-Joining Repair; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D015870:Gene Expression; D055786:Gene Knockout Techniques; D023061:Gene Order; D018390:Gene Targeting; D056426:Genetic Loci; D005822:Genetic Vectors; D059765:Homologous Recombination; D006720:Homozygote; D059785:Karyotype; D008297:Male; D006899:Mixed Function Oxygenases / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011485:Protein Binding; D013552:Swine / Q000235:genetics*; D016335:Zinc Fingers
chemical_list: D006899:Mixed Function Oxygenases; C074383:CMPacetylneuraminate monooxygenase