Mini-pigs as replacement for non-rodent species

K  Mohan; N Shridhar; S G Ramachandra; T V Shiva  Shankar; B H Pavithra; B Venkanna

doi:10.48165/jlas.2019.1.2.9

Authors

K Mohan Advinus Therapeutics Pvt. Ltd., Peenya 2nd Phase, Bangalore 560 058, India Author
N Shridhar Department of Pharmacology and Toxicology, Veterinary College, KVAFSU, Bangalore 560024, India Author
S G Ramachandra Principal Research Scientist, Indian Institute of Science, Bangalore 560 012, India Author
T V Shiva Shankar R&D Assistant, Molecular Biology and Genetics Unit, Jawaharlal Nehru Centre for Advanced Scientific Research, Bangalore 560064, India Author
B H Pavithra Department of Pharmacology and Toxicology, Veterinary College, KVAFSU, Bangalore 560024, India Author
B Venkanna Department of Pharmacology and Toxicology, Veterinary College, KVAFSU, Bangalore 560024, India Author

DOI:

https://doi.org/10.48165/jlas.2019.1.2.9

Keywords:

Minipig, xenografts, non- rodent, pharmacokinetic

Abstract

Swine is the optimal model species for investigation of a large number of human diseases and have made valuable contributions to almost every field of human medicine. Similarities in the cardiovascular, urogenital, integument, skeletal and digestive systems of swine to humans have contributed to increased use of pigs in research. Swine offer additional advantages over other species by having a renal anatomy and function very similar to human. Studies have lead to the development of a highly warranted vaccine for various diseases using swine as model. In animal models, whole cell vaccination resulted in hypersensitivity reactions, so new strategies are devised. The first immunogenic molecule described was the major outer membrane protein and this molecule has been studied in great detail as a candidate vaccine. Even though complete protection was not obtained, reduced shedding was observed and vaccine trials in SPF pigs as animal models using naked DNA as a vaccine resulted in stimulation of both the humoral and the cellular immune responses indicating progress in vaccine development. This model is also used in pharmacokinetic studies, evaluating ADME, interspecies variations in CYP subfamily. Further, because of their similarities with humans, pig tissues and organs are currently being used and studied as human xenografts with the potential for increased use in this area in the near future.

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References

Abelsth MK (1962). The application of specific pathogen-free animals to research and production. Can. Vet. J. 3:48-56.

Anzenbacher P, Soucek P, Anzenbacherová E, Gut I, Hrubý K, Svoboda Z, Kvĕtina J (1998). Presence and activity of cytochrome P450 isoforms in minipig liver microsomes. Comparison with human liver samples.

Drug Metab. Dispos. 26(1):56-59.

Bollen P, Ellegaard L (1997). The Göttingen minipig in pharmacology and toxicology. Pharmacol. Toxicol. 80(2): 3-4.

Daisy V, Thi QT, Hoang LDV, Kristel V, Taher H, Koen C, Servaas AM, Eric C (2005). Specific-Pathogen Free Pigs as an animal model for studying Chlamydia trachomatis genital infection. Infect. Immun. 73:8317– 8321.

Dehoux JP, Gianello P (2007). The importance of large animal models in transplantation. Front. Biosci.12:4864-4880.

Fiane AE, Mollnes TE (1999). Transplantation from animal to man Tidsskr. Nor. Laegeforen. 119 (28): 4213-4218.

Hamburger SA, Kopaciewicz LJ, Valocik RE (1991). A new model of myocardial infarction in Yucatan minipigs. J. Pharmacol. Methods. 25: 291–301.

Hughes HC (1986). Swine in cardiovascular research. Lab. Anim. Sci. 36: 348–350.

Kvetina J, Svoboda Z, Nobilis M, Pastera J, Anzenbacher P (1999). Experimental Goettingen minipig and Beagle dog as two species used in bioequivalence studies for clinical pharmacology. Gen. Physiol. Biophys. 18:80–

85.

Mahl JA, Vogel BE, Court M, Kolopp M, Roman D, Nogués V (2006). The minipig in dermatotoxicology: methods and challenges. Exp. Toxicol. Pathol. 57(5- 6):341-345.

Motlik J, Klíma J, Dvoránková B, Smetana K . (2007). Porcine epidermal stem cells as a biomedical model for wound healing and normal/malignant epithelial cell propagation. Theriogenol. 67(1):105-111.

Niemann H, Rath D (2001) Progress in reproductive biotechnology in swine. Theriogenol. 56(8): 1291-1304

Pavel Soucek, Roman Zuber, Eva Anzenbacherová, Pavel Anzenbacher, Peter Guengerich (2001). Minipig cytochrome P450 3A, 2A and 2C enzymes have similar properties to human analogs. BMC Pharmacol. 1: 11-15.

Rausch L, Bisinger E C, Sharma A, Rose R (2003). Use of the domestic Swine as an alternative animal model for conducting dermal irritation/corrosion studies on fatty amine ethoxylates. Int. J. Toxicol. 22(4):317-323.

Sampaio FJ, Pereira-Sampaio MA, Favorito LA (1998). The pig kidney as an endourologic model: anatomic contribution. J. Endourol. 12(1):45-50.

Skaanild MT, Friis C (1997). Characterization of the P450 system in Göttingen minipigs. Pharmacol. Toxicol. 80(2):28-33.

Skaanild MT, Friis C. (1999). Cytochrome P450 sex differences in minipigs and conventional pigs. Pharmacol. Toxicol. 85(4):174-180.

Skavlen PA, Stills HF, Caldwell CW, Middleton CC (1986). Malignant lymphoma in a Sinclair miniature pig. Am. J. Vet. Res. 47(2):389-393.

Smith AC, Spinale FG, Swindle MM (1990). Cardiac function and morphology of Hanford miniature swine and Yucatan miniature and micro swine. Lab. Anim. Sci. 40: 47–50.

Spurlock ME, Gabler NK (2008). The development of porcine models of obesity and the metabolic syndrome. J. Nutr. 138(2):397-402.

Svendsen O (2006). The minipig in toxicology. Exp. Toxicol. Pathol. 57(5-6): 335-339.

Swindle MM, Horneffer PJ, Gardner TJ, Gott VL, Hall TS, Sturat R S, Baumgartner WA, Borkon AM, Galloway E, Reitz BA (1986). Anatomic and anesthetic considerations

in experimental cardio-pulmonary surgery in swine. Lab. Anim. Sci. 36: 357–361.

Takeuchi Y, Magre S, Patience C (2005). The potential hazards of xenotransplantation: an overview. Rev. Sci Tech. 24(1):323-334.

Tetsuo N, Kazumato S,Toshiki S, Hajime Y, Keigo N, Yasuko B, Takuya H (2007). Use of miniature pig for biomedical research with reference to toxicological studies. J. Toxicol. Pathol.20:125-132.

Uchida M, Shimatsu Y, Onoe K, Matsuyama N, Niki R, Ikeda JE, Imai H. (2001). Production of transgenic miniature pigs by pronuclear microinjection. Transgenic Res. 10(6):577-582.

Vodicka P, Smetana K Jr, Dvoránková B, Emerick T, Xu YZ, Ourednik J, Ourednik V, Motlík J (2005). The miniature pig as an animal model in biomedical research. Ann. N Y. Acad. Sci. 1049: 161-171.

Wang S, Liu Y, Fang D, Shi S (2007). The miniature pig: a useful large animal model for dental and orofacial research. Oral Dis. 13(6):530-537.

Yamada K, Yazawa K, Shimizu A, Iwanaga T, Hisashi Y, Nuhn M, O’Malley P, Nobori S, Vagefi PA, Patience C, Fishman J, Cooper DKC, Hawley RJ, Greenstein J, Schuurman Henk-J, Awward M, Sykes M, Sachs DH. (2005). Marked prolongation of porcine renal xenograft survival in baboons through the use of α1,3-

galactosyltransferase gene-knockout donors and the cotransplantation of vasculized thymic tissue. Nat. Med. 11: 32–34.

Ye Y, Niekrasz M, Kosanke S, Welsh R (1994). The pig as a potential organ donor for man, a study of potentially transferable disease from donor pig to recipient man. Transplant. 57:694-703. .