Publications & Reports

Fucosyl transferase (H) transgenic heart transplants to Gal-/- mice.

McKenzie IF, Li YQ, Patton K, Sandrin MS
Molecular Immunogenetics Laboratory, Austin Research Institute, Austin and Repatriation Medical Centre, Heidelberg, Victoria, Australia.

Abstract

BACKGROUND: We have previously described the rejection of Gal+ mouse hearts by mice lacking Gala(1,3)Gal (Gal-/-) and demonstrated this to be a model of xenogeneic hyperacute rejection (HAR) which would occur in pig-to-human/primate xenotransplantation, where Gal+ antibody (Ab) and complement (C') mediate HAR. To reduce the amount of Gal present we used fucosyl transferase (H) as a transgene, H transferase competes for the same substrate as Gal transferase and reduces Gal expression by >90%. METHODS: Gal-/- mice received a heart graft from C57BL/6 Gal+ or H transgenic mice and additional Gal Ab and C' provided; HAR was monitored by direct observation for up to 90 min, or by palpation thereafter. When grafts were rejected they were examined macro- and microscopically. RESULTS: H transgenic mice were used as donors to Gal-/- mice; it was found that: 1) C57BL/6 or H transgenic hearts were not rejected by Gal-/- recipients within 90 min in the absence of additional Gal Ab. 2) If additional Gal Ab and C' were provided as fresh normal human serum (NHS), Gal+ (C57BL/6) grafts were rejected by Gal-/- mice in approximately 34 min, whereas H transgenic hearts mostly lasted up to 17 hr, but were then rejected. The histological appearances showed features of both Arthus and Shwartzmann phenomena. 3) Mice hyperimmunized with Gal with anti-Gal titers of >1:20,000, rejected Gal+ grafts in 31 min; the survival was prolonged to 75 min with the H transgenic hearts. CONCLUSION: The presence of the H transgene in donor hearts transplanted to naive Gal-/- mice delays the onset of HAR, but rejection ultimately occurs; if the mice are hyperimmune earlier rejection occurs. The expression of the H transgene alone is insufficient to avoid HAR in the Gal-/- mouse model; the presence of other transgenes and techniques will be required to give an appropriate increase in survival of pig-to-human/primate grafts.

Publication

  • Journal: Transplantation
  • Published: 27/10/2000
  • Volume: 70
  • Issue: 8
  • Pagination: 1205-1209