Production of α-1,3-galactosyltransferase null pigs by means of nuclear transfer with fibroblasts bearing loss of heterozygosity mutations

DOI Web Site 被引用文献20件
  • Donna Kolber-Simonds
    Immerge Biotherapeutics, Inc., 300 Technology Square, Cambridge, MA 02139; Department of Animal Science and Office of Animal Resources, University of Missouri, Columbia, MO 65211; Infigen, Inc., 1825 Infinity Drive, Deforest, WI 52532; and Transplantation Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02129
  • Liangxue Lai
    Immerge Biotherapeutics, Inc., 300 Technology Square, Cambridge, MA 02139; Department of Animal Science and Office of Animal Resources, University of Missouri, Columbia, MO 65211; Infigen, Inc., 1825 Infinity Drive, Deforest, WI 52532; and Transplantation Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02129
  • Steven R. Watt
    Immerge Biotherapeutics, Inc., 300 Technology Square, Cambridge, MA 02139; Department of Animal Science and Office of Animal Resources, University of Missouri, Columbia, MO 65211; Infigen, Inc., 1825 Infinity Drive, Deforest, WI 52532; and Transplantation Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02129
  • Maria Denaro
    Immerge Biotherapeutics, Inc., 300 Technology Square, Cambridge, MA 02139; Department of Animal Science and Office of Animal Resources, University of Missouri, Columbia, MO 65211; Infigen, Inc., 1825 Infinity Drive, Deforest, WI 52532; and Transplantation Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02129
  • Scott Arn
    Immerge Biotherapeutics, Inc., 300 Technology Square, Cambridge, MA 02139; Department of Animal Science and Office of Animal Resources, University of Missouri, Columbia, MO 65211; Infigen, Inc., 1825 Infinity Drive, Deforest, WI 52532; and Transplantation Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02129
  • Monica L. Augenstein
    Immerge Biotherapeutics, Inc., 300 Technology Square, Cambridge, MA 02139; Department of Animal Science and Office of Animal Resources, University of Missouri, Columbia, MO 65211; Infigen, Inc., 1825 Infinity Drive, Deforest, WI 52532; and Transplantation Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02129
  • Jeffery Betthauser
    Immerge Biotherapeutics, Inc., 300 Technology Square, Cambridge, MA 02139; Department of Animal Science and Office of Animal Resources, University of Missouri, Columbia, MO 65211; Infigen, Inc., 1825 Infinity Drive, Deforest, WI 52532; and Transplantation Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02129
  • David B. Carter
    Immerge Biotherapeutics, Inc., 300 Technology Square, Cambridge, MA 02139; Department of Animal Science and Office of Animal Resources, University of Missouri, Columbia, MO 65211; Infigen, Inc., 1825 Infinity Drive, Deforest, WI 52532; and Transplantation Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02129
  • Julia L. Greenstein
    Immerge Biotherapeutics, Inc., 300 Technology Square, Cambridge, MA 02139; Department of Animal Science and Office of Animal Resources, University of Missouri, Columbia, MO 65211; Infigen, Inc., 1825 Infinity Drive, Deforest, WI 52532; and Transplantation Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02129
  • Yanhong Hao
    Immerge Biotherapeutics, Inc., 300 Technology Square, Cambridge, MA 02139; Department of Animal Science and Office of Animal Resources, University of Missouri, Columbia, MO 65211; Infigen, Inc., 1825 Infinity Drive, Deforest, WI 52532; and Transplantation Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02129
  • Gi-Sun Im
    Immerge Biotherapeutics, Inc., 300 Technology Square, Cambridge, MA 02139; Department of Animal Science and Office of Animal Resources, University of Missouri, Columbia, MO 65211; Infigen, Inc., 1825 Infinity Drive, Deforest, WI 52532; and Transplantation Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02129
  • Zhonghua Liu
    Immerge Biotherapeutics, Inc., 300 Technology Square, Cambridge, MA 02139; Department of Animal Science and Office of Animal Resources, University of Missouri, Columbia, MO 65211; Infigen, Inc., 1825 Infinity Drive, Deforest, WI 52532; and Transplantation Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02129
  • Greg D. Mell
    Immerge Biotherapeutics, Inc., 300 Technology Square, Cambridge, MA 02139; Department of Animal Science and Office of Animal Resources, University of Missouri, Columbia, MO 65211; Infigen, Inc., 1825 Infinity Drive, Deforest, WI 52532; and Transplantation Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02129
  • Clifton N. Murphy
    Immerge Biotherapeutics, Inc., 300 Technology Square, Cambridge, MA 02139; Department of Animal Science and Office of Animal Resources, University of Missouri, Columbia, MO 65211; Infigen, Inc., 1825 Infinity Drive, Deforest, WI 52532; and Transplantation Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02129
  • Kwang-Wook Park
    Immerge Biotherapeutics, Inc., 300 Technology Square, Cambridge, MA 02139; Department of Animal Science and Office of Animal Resources, University of Missouri, Columbia, MO 65211; Infigen, Inc., 1825 Infinity Drive, Deforest, WI 52532; and Transplantation Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02129
  • August Rieke
    Immerge Biotherapeutics, Inc., 300 Technology Square, Cambridge, MA 02139; Department of Animal Science and Office of Animal Resources, University of Missouri, Columbia, MO 65211; Infigen, Inc., 1825 Infinity Drive, Deforest, WI 52532; and Transplantation Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02129
  • David J. J. Ryan
    Immerge Biotherapeutics, Inc., 300 Technology Square, Cambridge, MA 02139; Department of Animal Science and Office of Animal Resources, University of Missouri, Columbia, MO 65211; Infigen, Inc., 1825 Infinity Drive, Deforest, WI 52532; and Transplantation Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02129
  • David H. Sachs
    Immerge Biotherapeutics, Inc., 300 Technology Square, Cambridge, MA 02139; Department of Animal Science and Office of Animal Resources, University of Missouri, Columbia, MO 65211; Infigen, Inc., 1825 Infinity Drive, Deforest, WI 52532; and Transplantation Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02129
  • Erik J. Forsberg
    Immerge Biotherapeutics, Inc., 300 Technology Square, Cambridge, MA 02139; Department of Animal Science and Office of Animal Resources, University of Missouri, Columbia, MO 65211; Infigen, Inc., 1825 Infinity Drive, Deforest, WI 52532; and Transplantation Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02129
  • Randall S. Prather
    Immerge Biotherapeutics, Inc., 300 Technology Square, Cambridge, MA 02139; Department of Animal Science and Office of Animal Resources, University of Missouri, Columbia, MO 65211; Infigen, Inc., 1825 Infinity Drive, Deforest, WI 52532; and Transplantation Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02129
  • Robert J. Hawley
    Immerge Biotherapeutics, Inc., 300 Technology Square, Cambridge, MA 02139; Department of Animal Science and Office of Animal Resources, University of Missouri, Columbia, MO 65211; Infigen, Inc., 1825 Infinity Drive, Deforest, WI 52532; and Transplantation Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02129

抄録

<jats:p> Hyperacute rejection of porcine organs by old world primate recipients is mediated through preformed antibodies against galactosyl-α-1,3-galactose (Galα-1,3-Gal) epitopes expressed on the pig cell surface. Previously, we generated inbred miniature swine with a null allele of the α-1,3-galactosyltransferase locus ( <jats:italic>GGTA1</jats:italic> ) by nuclear transfer (NT) with gene-targeted fibroblasts. To expedite the generation of <jats:italic>GGTA1</jats:italic> null pigs, we selected spontaneous null mutant cells from fibroblast cultures of heterozygous animals for use in another round of NT. An unexpectedly high rate of spontaneous loss of <jats:italic>GGTA1</jats:italic> function was observed, with the vast majority of null cells resulting from loss of the WT allele. Healthy piglets, hemizygous and homozygous for the gene-targeted allele, were produced by NT by using fibroblasts that had undergone deletional and crossover/gene conversion events, respectively. Aside from loss of Galα-1,3-Gal epitopes, there were no obvious phenotypic differences between these null piglets and WT piglets from the same inbred lines. In fact, congenital abnormalities observed in the heterozygous NT animals did not reappear in the serially produced null animals. </jats:p>

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