Transgenic pigs as models for translational biomedical research. J Mol Med (Berl)
The translation of novel discoveries from basic research to clinical application is a long, often inefficient, and thus costly process. Accordingly, the process of drug development requires optimization both for economic and for ethical reasons, in order to provide patients with appropriate treatments in a reasonable time frame. Consequently, "Translational Medicine" became a top priority in national and international roadmaps of human health research. Appropriate animal models for the evaluation of efficacy and safety of new drugs or therapeutic concepts are critical for the success of translational research. In this context rodent models are most widely used. At present, transgenic pigs are increasingly being established as large animal models for selected human diseases. The first pig whole genome sequence and many other genomic resources will be available in the near future. Importantly, efficient and precise techniques for the genetic modification of pigs have been established, facilitating the generation of tailored disease models. This article provides an overview of the current techniques for genetic modification of pigs and the transgenic pig models established for neurodegenerative diseases, cardiovascular diseases, cystic fibrosis, and diabetes mellitus.
[Show abstract] [Hide abstract] ABSTRACT: This article provides guidelines for organ and tissue sampling adapted to porcine animal models in translational medical research. Detailed protocols for the determination of sampling locations and numbers as well as recommendations on the orientation, size, and trimming direction of samples from ∼50 different porcine organs and tissues are provided in the Supplementary Material. The proposed sampling protocols include the generation of samples suitable for subsequent qualitative and quantitative analyses, including cryohistology, paraffin, and plastic histology; immunohistochemistry; in situ hybridization; electron microscopy; and quantitative stereology as well as molecular analyses of DNA, RNA, proteins, metabolites, and electrolytes. With regard to the planned extent of sampling efforts, time, and personnel expenses, and dependent upon the scheduled analyses, different protocols are provided. These protocols are adjusted for (I) routine screenings, as used in general toxicity studies or in analyses of gene expression patterns or histopathological organ alterations, (II) advanced analyses of single organs/tissues, and (III) large-scale sampling procedures to be applied in biobank projects. Providing a robust reference for studies of porcine models, the described protocols will ensure the efficiency of sampling, the systematic recovery of high-quality samples representing the entire organ or tissue as well as the intra-/interstudy comparability and reproducibility of results.0Comments 1Citation
- "The respective protocols are designed to fit the demands of the industrial standards of the pharmaceutical industry and toxicologic pathology. They have been developed based on extensive experiences in pig toxicopathology, in pathomorphological characterization of numerous genetically modified pig models, and in porcine animal model biobanking (Abbott 2015; Aigner et al. 2010; Kemter et al. 2012; Klymiuk et al. 2013; Klymiuk et al. 2012a; Klymiuk et al. 2012b; Klymiuk et al. 2012c; Renner et al. 2010 Renner et al. , 2012 Renner et al. , 2013 Streckel et al. 2015; Wuensch et al. 2014). The proposed sampling protocols are intended as general guidelines but not as requirements for the sampling of tissues in any porcine model. "
[Show abstract] [Hide abstract] ABSTRACT: One of the most powerful strategies to investigate biology we have as scientists, is the ability to transfer genetic material in a controlled and deliberate manner between organisms. When applied to livestock, applications worthy of commercial venture can be devised. Although initial methods used to generate transgenic livestock resulted in random transgene insertion, the development of SCNT technology enabled homologous recombination gene targeting strategies to be used in livestock. Much has been accomplished using this approach. However, now we have the ability to change a specific base in the genome without leaving any other DNA mark, with no need for a transgene. With the advent of the genome editors this is now possible and like other significant technological leaps, the result is an even greater diversity of possible applications. Indeed, in merely 5 years, these 'molecular scissors' have enabled the production of more than 300 differently edited pigs, cattle, sheep and goats. The advent of genome editors has brought genetic engineering of livestock to a position where industry, the public and politicians are all eager to see real use of genetically engineered livestock to address societal needs. Since the first transgenic livestock reported just over three decades ago the field of livestock biotechnology has come a long way-but the most exciting period is just starting.0Comments 1Citation
- "Genome editing enables the mutation of endogenous livestock gene homologues of known causative or associated human disease loci. Although there are no projects yet that have fully exploited this new technology, there are already a growing number of projects based on the 'older' transgenic technologies that have demonstrated that this belief in large animal disease models is justified (Wolf et al. 2014; Aigner et al. 2010). "
[Show abstract] [Hide abstract] ABSTRACT: Genetic modification of livestock proves beneficial to human health by economic and efficient production of important pharmaceutical proteins and to study human diseases. The creation of transgenic animals has resulted in the more use of laboratory animal such as mice instead of large size animals and has decreased the number of animals used in experiment related to the development of disease models. Since, transgenic technology has great potential in many fields including livestock, medicine and industry. Several methods have been used for the production of transgenic animals like Microinjection of fertilized ovum, Embryonic stem (ES) cells mediated gene transfer and Retrovirus-mediated gene transfer.0Comments 0Citations
- "Transgenic fish shows increased growth rate, improved flesh color and increased disease resistance than the natural fish. Transgenic pigs used as an animal model of human diseases like cancer, Alzheimer's disease, cardiovascular diseases, cystic fibrosis and diabetes mellitus (Aigner et al., 2010). Transgenic pigs take care of the environmental issue of manure based phosphorous pollution and serve as donors in human organ transplantation (i.e. "