Microbiological characterization of Göttingen minipigs
Authors: Denner Joachim 
Published: April 2014

Xenotransplantation using pig cells, tissues or organs may be associated with transmission of porcine microorganisms which in the worst case scenario may induce zoonoses. To prevent this, a detailed analysis of the viruses, bacteria, fungi and protozoa in the donor pigs should be performed. This includes characterization of the herd as well as of each individual donor animal. Furthermore, the final transplant, e.g., the islet cell preparation, should be analyzed.At present, the Auckland island pigs are the best characterized animals and the presence of numerous bacteria, viruses and protozoa is analyzed regularly in the animals and in islet cell preparations [1]. Preclinical [2] and clinical [3] trials transplanting islet cells from these animals did not result in transmission of porcine microorganisms including the porcine endogenous retroviruses (PERVs). PERV‐A and PERV‐B are present in the genome of all pigs, and they may infect human cells (for review see [4]). PERV‐C are not present in all pigs, they infect only pig cells, however recombinant PERV‐A/C infect human cells and are characterized by high replication rates. Previously it was shown that the expression of PERVs was different among breeds including German landrace, Duroc, Schwäbisch‐Hällisch, Large White, as well as (multi)transgenic crossbreds generated for xenotransplantation [5]. The highest expression was found in Yucatan minipigs [6]. Although PERV expression was well studied in these breeds, the prevalence of other microorganisms remains unclear.In addition to the Auckland island pigs the Göttingen minipigs, which are held at Ellegaard, Denmark, represent another well‐characterized pig breed. The animals are well‐defined concerning their physiologic parameters, health status, and genetics since this herd was established with the purpose to supply minipigs for preclinical pharmacology and toxicology [7]. Health monitoring includes testing for a broad spectrum of viruses, bacteria, fungi and protozoa and health reports are regularly published at Ellegaard website [8]. When the prevalence and the expression of PERVs were analyzed in these animals, it was demonstrated that although PERV‐A, ‐B and ‐C proviruses were found in all animals, their expression was low [9]. Unfortunately the health monitoring of the herd does not include xenozoonotic infectious agents such as cytomegalovirus, gamma‐lymphotropic herpesvirus and hepatitis E [10]. Approaches to detect these viruses are under development and additional investigations are required to assess the suitability of Göttingen minipigs and other animals for xenotransplantation in terms of microbiological safety.References[1] Wynyard S, Nathu D, Garkavenko O, Denner J, Elliott R. Microbiological safety of the first clinical pig islet xenotransplantation trial in New Zealand. submitted.[2] Garkavenko O, Dieckhoff B, Wynyard S et al. Absence of transmission of potentially xenotic viruses in a prospective pig to primate islet xenotransplantation study. J Med Virol. 2008; 80(11): 2046–2052.[3] Garkavenko O, Croxson MC, Irgang M et al. Monitoring for presence of potentially xenotic viruses in recipients of pig islet xenotransplantation. J Clin Microbiol. 2004; 42(11): 5353–5356.[4] Denner J, Tönjes RR. Infection barriers to successful xenotransplantation focusing on porcine endogenous retroviruses. Clin Microbiol Rev. 2012; 25(2): 318–343.[5] Dieckhoff B, Kessler B, Jobst D et al. Distribution and expression of porcine endogenous retroviruses in multi‐transgenic pigs generated for xenotransplantation. Xenotransplantation. 2009; 16(2): 64–73.[6] Bittmann I, Mihica D, Plesker R, Denner J. Expression of porcine endogenous retroviruses (PERV) in different organs of a pig. Virology. 2012; 433(2): 329–336.[7] Mcanulty PA, Dayan AD, Ganderup NC, Hastings KH, eds: The Minipig in Biomedical Research. Boca Raton, CRC Press, Taylor and Francis, 2012.[8] Ellegaard Göttingen Minipigs. http://www.minipigs.dk. Accessed March 11, 2013.[9] Semaan M, Rotem A, Barkai U, Bornstein S, Denner J. Screening pigs for xenotransplantation: prevalence and expression of porcine endogenous retroviruses in Göttingen minipigs. Xenotransplantation 2013; 20: 148–156.[10] Schuurman H‐J, Patience C. Commentary. Screening pigs for xenotransplantation: Prevalence and expression of porcine endogenous retroviruses (PERVs) in Göttingen minipigs. Xenotransplantation 2013; 20: 135–137.