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小型猪作为毒理学新技术的平台。

The minipig as a platform for new technologies in toxicology.

作者信息

Forster Roy, Ancian Philippe, Fredholm Merete, Simianer Henner, Whitelaw Bruce

机构信息

CIT, BP 563, 27000 Evreux, France.

出版信息

J Pharmacol Toxicol Methods. 2010 Nov-Dec;62(3):227-35. doi: 10.1016/j.vascn.2010.05.007. Epub 2010 May 31.

Abstract

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 Göttingen 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.

摘要

本文综述了小型猪作为基因组学、高密度生物学、转基因技术、体外毒理学及相关新兴技术未来发展平台的潜力。猪作为农业生产物种所具有的商业利益推动了这些领域的科学进步。而对于狗和猴子来说,却没有类似的经济驱动力来推动其在这些领域的进展。因此,在许多领域(生理学、疾病、遗传学、免疫学等),猪的现有知识基础(相比狗和猴子)要丰富得多。猪的基础基因组知识和表型特征远远领先于狗和猴子,所以猪的基础知识很可能继续领先于这两个物种。虽然新兴技术本质上是“物种中性”的,原则上可以应用于所有物种,但就我们所研究的所有技术而言,猪的基础知识和技术能力比狗或猴子更强。具体而言,在安全测试应用方面,我们发现:(i)哥廷根小型猪非常适合进行毒理基因组学研究;(ii)猪与人之间紧密的序列同源性表明小型猪将有助于生物技术产品的测试(可能也适用于计算机模拟毒理学);(iii)小型猪是唯一一种能够轻松培育转基因动物的非啮齿类毒理学模型,并且猪的生殖技术也很发达。这些特性也应该使小型猪成为测试生物技术产品的一个有吸引力的模型。所有这些因素都支持这样一种观点,即小型猪完全有能力应对新兴技术和未来毒理学的挑战;小型猪似乎也有可能成为测试生物技术产品的一个优势模型。

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