title: Characterization of pigs transgenic for human decay-accelerating factor.
abstract: BACKGROUND
  To prevent the central role played by complement activation in the hyperacute rejection of pig organs transplanted into primates, pigs transgenic for human decay-accelerating factor (HDAF) have recently been produced. The data presented here extend previous immunohistochemical findings by documenting the immunological characterization and the levels of expression of HDAF in these transgenic pigs.
  
  
  METHODS
  Animals from 30 independently derived lines were included in this study. HDAF expression was characterized by immunoprecipitation and epitope mapping. Quantitative analysis was performed by radiometric assays followed by Scatchard analysis and by double-determinant radioimmunoassay. Deposition of iC3b on porcine aortic endothelial cells was determined by radioimmunoassay. DNA slot-blot analysis and densitometric scanning were used to evaluate HDAF transgene copy number.
  
  
  RESULTS
  The integrity of HDAF expressed by these transgenic pigs could be demonstrated. HDAF was present in 72% of the organs analyzed, although considerable variation in expression occurred, both between animals and within the same pig. High levels of HDAF on porcine aortic endothelial cells resulted in iC3b deposition at levels as low as that detected on human endothelial cells. Twenty-six organs expressed levels of HDAF greater than those observed in the equivalent human tissue. HDAF expression did not correlate with the number of copies of the transgene incorporated into the porcine genome.
  
  
  CONCLUSIONS
  Transgenic pigs, which express levels of functional HDAF even greater than those observed in humans, have successfully been produced. Pigs transgenic for human complement inhibiting molecules could represent a source of organs for future clinical xenotransplantation.
authors.affiliation: Department of Surgery, University of Cambridge, and Imutran Ltd. (A Novartis Pharma AG Company), England.
authors.forename: E
authors.initials: E
authors.lastname: Cozzi
authors.forename: A W
authors.initials: AW
authors.lastname: Tucker
authors.forename: G A
authors.initials: GA
authors.lastname: Langford
authors.forename: G
authors.initials: G
authors.lastname: Pino-Chavez
authors.forename: L
authors.initials: L
authors.lastname: Wright
authors.forename: M J
authors.initials: MJ
authors.lastname: O'Connell
authors.forename: V J
authors.initials: VJ
authors.lastname: Young
authors.forename: R
authors.initials: R
authors.lastname: Lancaster
authors.forename: M
authors.initials: M
authors.lastname: McLaughlin
authors.forename: K
authors.initials: K
authors.lastname: Hunt
authors.forename: M C
authors.initials: MC
authors.lastname: Bordin
authors.forename: D J
authors.initials: DJ
authors.lastname: White
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified / Q000235:genetics; D001011:Aorta; D001706:Biopsy; D018958:CD55 Antigens / Q000235:genetics* / Q000494:pharmacology; D003167:Complement Activation / Q000276:immunology; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D007124:Immunoenzyme Techniques; D009132:Muscles / Q000378:metabolism / Q000473:pathology; D011863:Radioimmunoassay / Q000379:methods; D013552:Swine; D014018:Tissue Distribution; D019076:Transgenes / Q000235:genetics; D014183:Transplantation, Heterologous
chemical_list: D018958:CD55 Antigens