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Use of the CRISPR/Cas9 system to produce genetically engineered pigs from in vitro-derived oocytes and embryos.
Whitworth, Kristin M; Lee, Kiho; Benne, Joshua A; Beaton, Benjamin P; Spate, Lee D; Murphy, Stephanie L; Samuel, Melissa S; Mao, Jiude; O'Gorman, Chad; Walters, Eric M; Murphy, Clifton N; Driver, John; Mileham, Alan; McLaren, David; Wells, Kevin D; Prather, Randall S.
Afiliación
  • Whitworth KM; Division of Animal Science, University of Missouri-Columbia, Columbia, Missouri.
  • Lee K; Division of Animal Science, University of Missouri-Columbia, Columbia, Missouri.
  • Benne JA; Division of Animal Science, University of Missouri-Columbia, Columbia, Missouri.
  • Beaton BP; National Swine Resource and Research Center, University of Missouri-Columbia, Columbia, Missouri.
  • Spate LD; Division of Animal Science, University of Missouri-Columbia, Columbia, Missouri National Swine Resource and Research Center, University of Missouri-Columbia, Columbia, Missouri.
  • Murphy SL; Division of Animal Science, University of Missouri-Columbia, Columbia, Missouri.
  • Samuel MS; Division of Animal Science, University of Missouri-Columbia, Columbia, Missouri National Swine Resource and Research Center, University of Missouri-Columbia, Columbia, Missouri.
  • Mao J; National Swine Resource and Research Center, University of Missouri-Columbia, Columbia, Missouri.
  • O'Gorman C; National Swine Resource and Research Center, University of Missouri-Columbia, Columbia, Missouri.
  • Walters EM; National Swine Resource and Research Center, University of Missouri-Columbia, Columbia, Missouri.
  • Murphy CN; Division of Animal Science, University of Missouri-Columbia, Columbia, Missouri.
  • Driver J; University of Florida, Gainesville, Florida.
  • Mileham A; Genus, plc, DeForest, Wisconsin.
  • McLaren D; Genus, plc, DeForest, Wisconsin.
  • Wells KD; Division of Animal Science, University of Missouri-Columbia, Columbia, Missouri National Swine Resource and Research Center, University of Missouri-Columbia, Columbia, Missouri.
  • Prather RS; Division of Animal Science, University of Missouri-Columbia, Columbia, Missouri National Swine Resource and Research Center, University of Missouri-Columbia, Columbia, Missouri pratherr@missouri.edu.
Biol Reprod ; 91(3): 78, 2014 Sep.
Article en En | MEDLINE | ID: mdl-25100712
Targeted modification of the pig genome can be challenging. Recent applications of the CRISPR/Cas9 system hold promise for improving the efficacy of genome editing. When a designed CRISPR/Cas9 system targeting CD163 or CD1D was introduced into somatic cells, it was highly efficient in inducing mutations. When these mutated cells were used with somatic cell nuclear transfer, offspring with these modifications were created. When the CRISPR/Cas9 system was delivered into in vitro produced presumptive porcine zygotes, the system was effective in creating mutations in eGFP, CD163, and CD1D (100% targeting efficiency in blastocyst stage embryos); however, it also presented some embryo toxicity. We could also induce deletions in CD163 or CD1D by introducing two types of CRISPRs with Cas9. The system could also disrupt two genes, CD163 and eGFP, simultaneously when two CRISPRs targeting two genes with Cas9 were delivered into zygotes. Direct injection of CRISPR/Cas9 targeting CD163 or CD1D into zygotes resulted in piglets that have mutations on both alleles with only one CD1D pig having a mosaic genotype. We show here that the CRISPR/Cas9 system can be used by two methods. The system can be used to modify somatic cells followed by somatic cell nuclear transfer. System components can also be used in in vitro produced zygotes to generate pigs with specific genetic modifications.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Oocitos / Blastocisto / Animales Modificados Genéticamente / Ingeniería Genética / Sus scrofa / Embrión de Mamíferos / Sistemas CRISPR-Cas Límite: Animals Idioma: En Revista: Biol Reprod Año: 2014 Tipo del documento: Article Pais de publicación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Oocitos / Blastocisto / Animales Modificados Genéticamente / Ingeniería Genética / Sus scrofa / Embrión de Mamíferos / Sistemas CRISPR-Cas Límite: Animals Idioma: En Revista: Biol Reprod Año: 2014 Tipo del documento: Article Pais de publicación: Estados Unidos