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A human CD46 transgenic pig model system for the study of discordant xenotransplantation.

Publication ,  Journal Article
Diamond, LE; Quinn, CM; Martin, MJ; Lawson, J; Platt, JL; Logan, JS
Published in: Transplantation
January 15, 2001

BACKGROUND: The chronic shortage in the supply of human organs available for allotransplantation has turned attention toward the use of animals as potential donors, with pigs as the most likely species under consideration. Hyperacute rejection, the initial and immediate barrier to a pig-to-primate xenograft, has been addressed by generation of transgenic pigs that express the human membrane-bound complement-regulatory proteins CD59 and/or CD55. Difficulty has been encountered in generation of transgenic animals that express a third membrane-bound complement-regulatory protein, CD46. METHODS: We have generated transgenic animals by using a large genomic construct that encompasses the entire human CD46 gene. RESULTS: We report the first description of transgenic mice and pigs that express high levels of human CD46 in a cell and tissue type-specific manner, resembling patterns of endogenous CD46 expression observed in human tissues. Furthermore, when human CD46 transgenic porcine hearts were transplanted into baboons, the grafts did not succumb to hyperacute rejection, and survival extended for up to 23 days. Under the same conditions, nontransgenic grafts underwent hyperacute rejection within 90 min. CONCLUSIONS: This is the first report to describe generation of transgenic pigs that express human CD46, and the first in vivo demonstration of the ability of human CD46 expressed on pig organs to regulate complement activation and overcome hyperacute rejection upon transplantation of a vascularized organ into nonhuman primates.

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Published In

Transplantation

DOI

ISSN

0041-1337

Publication Date

January 15, 2001

Volume

71

Issue

1

Start / End Page

132 / 142

Location

United States

Related Subject Headings

  • Transplantation, Heterologous
  • Swine
  • Surgery
  • Reverse Transcriptase Polymerase Chain Reaction
  • Protein Isoforms
  • Organ Transplantation
  • Mice, Transgenic
  • Mice
  • Membrane Glycoproteins
  • Membrane Cofactor Protein
 

Citation

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Diamond, L. E., Quinn, C. M., Martin, M. J., Lawson, J., Platt, J. L., & Logan, J. S. (2001). A human CD46 transgenic pig model system for the study of discordant xenotransplantation. Transplantation, 71(1), 132–142. https://doi.org/10.1097/00007890-200101150-00021
Diamond, L. E., C. M. Quinn, M. J. Martin, J. Lawson, J. L. Platt, and J. S. Logan. “A human CD46 transgenic pig model system for the study of discordant xenotransplantation.Transplantation 71, no. 1 (January 15, 2001): 132–42. https://doi.org/10.1097/00007890-200101150-00021.
Diamond LE, Quinn CM, Martin MJ, Lawson J, Platt JL, Logan JS. A human CD46 transgenic pig model system for the study of discordant xenotransplantation. Transplantation. 2001 Jan 15;71(1):132–42.
Diamond, L. E., et al. “A human CD46 transgenic pig model system for the study of discordant xenotransplantation.Transplantation, vol. 71, no. 1, Jan. 2001, pp. 132–42. Pubmed, doi:10.1097/00007890-200101150-00021.
Diamond LE, Quinn CM, Martin MJ, Lawson J, Platt JL, Logan JS. A human CD46 transgenic pig model system for the study of discordant xenotransplantation. Transplantation. 2001 Jan 15;71(1):132–142.

Published In

Transplantation

DOI

ISSN

0041-1337

Publication Date

January 15, 2001

Volume

71

Issue

1

Start / End Page

132 / 142

Location

United States

Related Subject Headings

  • Transplantation, Heterologous
  • Swine
  • Surgery
  • Reverse Transcriptase Polymerase Chain Reaction
  • Protein Isoforms
  • Organ Transplantation
  • Mice, Transgenic
  • Mice
  • Membrane Glycoproteins
  • Membrane Cofactor Protein