The minipig as a platform for new technologies in toxicology

被引:62
作者
Forster, Roy [1 ]
Ancian, Philippe [1 ]
Fredholm, Merete [2 ]
Simianer, Henner [3 ]
Whitelaw, Bruce [4 ]
机构
[1] CIT, F-27000 Evreux, France
[2] Royal Vet & Agr Univ, Dept Anim Sci & Anim Hlth, DK-1870 Frederiksberg C, Denmark
[3] Univ Gottingen, Inst Anim Husb & Genet, D-37075 Gottingen, Germany
[4] Univ Edinburgh, Div Dev Biol, Roslin Inst, Roslin EH25 9PZ, Midlothian, Scotland
基金
英国生物技术与生命科学研究理事会;
关键词
Minipig; Methods; RETHINK; Toxicology; Genomics; Gene manipulation; TRANSGENIC PIGS; GENE-TRANSFER; STEM-CELLS; EXPRESSION; PORCINE; GENERATION; MUTATION; OOCYTES; MUSCLE; GROWTH;
D O I
10.1016/j.vascn.2010.05.007
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
The potential of the minipig as a platform for future developments in genomics, high density biology, transgenic technology, in vitro toxicology and related emerging technologies was reviewed. Commercial interests in the pig as an agricultural production species have driven scientific progress in these areas. There is no equivalent economic driver for progress in the dog or the monkey. As a result the available knowledge-bases are much greater for pigs (than for dogs or monkeys) in many areas (physiology, disease, genetics, immunology etc). Fundamental genomic knowledge and phenotypic characterization in regard to the pig is well in advance of the dog or the monkey and basic knowledge of the pig is therefore likely to stay ahead of the other two species. While the emerging technologies are essentially "species neutral" and can in principle be applied to all species, for all the technologies that we examined, basic knowledge and technical capabilities are greater for the pig than the dog or monkey. In concrete terms, in application to safety testing we have seen that: (i) The Gottingen minipig is well positioned for the performance of toxicogenomics studies, (ii) The close sequence homology between pigs and humans suggest that minipigs will be useful for the testing of biotechnology products (and possibly for in silico toxicology) and (iii) the minipig is the only non-rodent toxicology model where transgenic animals can be readily generated, and reproductive technologies are well developed in the pig. These properties should also make the minipig an interesting model for the testing of biotechnology products. These factors all support the idea that the minipig is well placed to meet the challenges of the emerging technologies and the toxicology of the future: it also seems likely that the minipig can be an advantageous model for the testing of biotechnology products. (C) 2010 Elsevier Inc. All rights reserved.
引用
收藏
页码:227 / 235
页数:9
相关论文
共 62 条
[1]   GENETIC-MAPPING OF QUANTITATIVE TRAIT LOCI FOR GROWTH AND FATNESS IN PIGS [J].
ANDERSSON, L ;
HALEY, CS ;
ELLEGREN, H ;
KNOTT, SA ;
JOHANSSON, M ;
ANDERSSON, K ;
ANDERSSONEKLUND, L ;
EDFORSLILJA, I ;
FREDHOLM, M ;
HANSSON, I ;
HAKANSSON, J ;
LUNDSTROM, K .
SCIENCE, 1994, 263 (5154) :1771-1774
[2]   Reciprocal chromosome painting reveals detailed regions of conserved synteny between the karyotypes of the domestic dog (Canis familiaris) and human [J].
Breen, M ;
Thomas, R ;
Binns, MM ;
Carter, NP ;
Langford, CF .
GENOMICS, 1999, 61 (02) :145-155
[3]  
Brem G, 1989, Tierarztl Prax Suppl, V4, P31
[4]   Xenotransplantation:: an update on recent progress and future perspectives [J].
Bucher, P ;
Morel, P ;
Bühler, LH .
TRANSPLANT INTERNATIONAL, 2005, 18 (08) :894-901
[5]   Producing primate embryonic stem cells by somatic cell nuclear transfer [J].
Byrne, J. A. ;
Pedersen, D. A. ;
Clepper, L. L. ;
Nelson, M. ;
Sanger, W. G. ;
Gokhale, S. ;
Wolf, D. P. ;
Mitalipov, S. M. .
NATURE, 2007, 450 (7169) :497-U3
[6]   Transgenic monkeys produced by retroviral gene transfer into mature oocytes [J].
Chan, AWS ;
Chong, KY ;
Martinovich, C ;
Simerly, C ;
Schatten, G .
SCIENCE, 2001, 291 (5502) :309-312
[7]   A future for transgenic livestock [J].
Clark, J ;
Whitelaw, B .
NATURE REVIEWS GENETICS, 2003, 4 (10) :825-833
[8]   Health status of transgenic pigs expressing the human complement regulatory protein CD59 [J].
Deppenmeier, Stefanie ;
Bock, Oliver ;
Mengel, Michael ;
Niemann, Heiner ;
Kues, Wilfried ;
Lemme, Erika ;
Wirth, Dagmar ;
Wonigeit, Kurt ;
Kreipe, Hans .
XENOTRANSPLANTATION, 2006, 13 (04) :345-356
[9]   The RETHINK project Minipigs as models for the toxicity testing of new medicines and chemicals: an impact assessment [J].
Forster, Roy ;
Bode, Gerd ;
Ellegaard, Lars ;
van der Laan, Jan Willem .
JOURNAL OF PHARMACOLOGICAL AND TOXICOLOGICAL METHODS, 2010, 62 (03) :158-159
[10]   The RETHINK project on minipigs in the toxicity testing of new medicines and chemicals: Conclusions and recommendations [J].
Forster, Roy ;
Bode, Gerd ;
Ellegaard, Lars ;
van der Laan, Jan-Willem .
JOURNAL OF PHARMACOLOGICAL AND TOXICOLOGICAL METHODS, 2010, 62 (03) :236-242