ORTHOTOPIC LIVER TRANSPLANTATION IN THE MOUSE

Abstract

Heart and kidney transplantation in the mouse has been well established (1, 2), but orthotopic liver transplantation has not been reported. Although the mouse is one-tenth the size of the rat, there are many advantages to using the mouse for immunologic research. The mouse genome has been more thoroughly characterized than the rat or any other species of mammal. The mouse H-2 system also bears a striking resemblance to the human HLA system. In addition, there are numerous genetically defined inbred strains and wealth of monoclonal antibodies that are commercially available for mouse investigations. A key development in rat orthotopic liver transplantation (3) was the introduction by Zimmerman et al. (4) and Kamada and Caine (5), of the cuff technique instead of suture for some of the venous vascular anastomoses. This method shortened the clamping time of the portal vein and increased survival. We have applied this principle to mouse orthotopic liver transplantation. In our pilot studies, more than 40 syngeneic mouse liver replacements were performed before 6 long-term survivors were obtained. The experience reported here is with the next 48 attempts, in which the surgical success rate was 83%. Male inbred syngeneic mice 10–12 weeks old (25–32 g), from Jackson Laboratory, Bar Harbor, ME, were used as size-matched donors and recipients under methoxyflurane (2.2-dichloro-1,1-difluoroethyl methyl ether) anesthesia. The strains used were B6AF1 (27 pairs), C57BL/6 (11 pairs), and BALB/c (10 pairs). Clean but not sterile operative technique was used, and all procedures were performed under the operating microscope with 4–6.4× magnification.