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Related Experiment Videos

Characterization of pigs transgenic for human decay-accelerating factor

E Cozzi1, A W Tucker, G A Langford

  • 1Department of Surgery, University of Cambridge, and Imutran Ltd. (A Novartis Pharma AG Company), England.

Transplantation
|December 10, 1997
PubMed
Summary

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Transgenic pigs expressing functional human decay-accelerating factor (HDAF) were developed to prevent organ rejection. These pigs show high HDAF levels, making them promising for xenotransplantation.

Area of Science:

  • Xenotransplantation research
  • Transgenic animal models
  • Complement system biology

Background:

  • Complement activation is a key barrier in pig-to-primate xenotransplantation.
  • Transgenic pigs expressing human decay-accelerating factor (HDAF) have been created to overcome this barrier.

Purpose of the Study:

  • To immunologically characterize and quantify HDAF expression in transgenic pigs.
  • To assess the functional capacity of HDAF in preventing complement-mediated damage.

Main Methods:

  • Immunoprecipitation, epitope mapping, and radiometric assays for HDAF characterization.
  • Radioimmunoassay to measure iC3b deposition on cells.
  • DNA slot-blot analysis for transgene copy number evaluation.

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Main Results:

  • Functional HDAF was successfully expressed in transgenic pigs.
  • 72% of analyzed organs showed HDAF expression with significant inter- and intra-animal variation.
  • High HDAF levels on porcine cells reduced iC3b deposition to levels comparable to human cells.
  • HDAF expression did not correlate with transgene copy number.

Conclusions:

  • Transgenic pigs expressing functional HDAF at levels exceeding human expression have been generated.
  • These pigs represent a potential source for organs in future clinical xenotransplantation.