【Animal Modeling】-The establishment and application of genetic modification tool pig model

  Transgenic animals are animal strains obtained through artificial mutation. This can be achieved by transferring foreign genes or mutating genes in animals. Tool animal models refer to animal models established by modifying known genes, which can be used as tools to help achieve other target gene modifications. In mice, many genetically modified tool models have been established and used, including stem cell marker mouse models (OG2 transgenic mice), Cre/loxP genetically modified mice and immunodeficient mice.

  These tool mouse models greatly facilitate research. Advances in life sciences and biomedicine. The pig is not only one of the main economic animals in agriculture, but also has a wide range of uses in the field of biomedicine. First, pigs are a good animal model for human diseases. The cardiovascular system, digestive system, skin, nutritional requirements, bone development and mineral metabolism of pigs are very similar to humans. The pig's size and taming habits allow for repeatability. Sampling, the breeding cycle is short, the productivity is high, and the litter produces a lot of litter. Transgenic experimental animal models play an important role in the study of genetic functions related to human diseases, the relationship between disease phenotypes and genotypes, disease diagnosis and treatment, and can also be used as important drug evaluation models. Third, pigs are ideal donors for allogeneic organ transplantation. Using transgenic technology to transform the genetic characteristics of heterologous organs to make them suitable for human organ or tissue transplantation is the most effective way to solve the shortage of organ transplantation.

  Like mice, genetically modified organisms promote the rapid realization of the application value of the above pigs by establishing tool pigs for various applications. The establishment of genetic engineering tool animals usually involves the application of multi-gene transfer and multi-step gene targeting technology. However, no porcine embryonic stem cells have been established so far. Porcine induced pluripotent stem cells prepared by induced pluripotent stem cell technology do not have germline mosaic ability. The preparation of transgenic pigs is mainly accomplished by combining somatic cell gene modification and somatic cell nuclear transfer technology.

  Due to the limited proliferation capacity of somatic cells and the low efficiency of gene modification, especially gene targeting, it is very difficult to use gene modification tools to establish pig models. In recent years, the development of Cas9 nucleic acid through artificial endonucleases ZFN, TALEN, RNAs has brought a revolutionary breakthrough in gene knockout technology, solved the problem of target modification and genetic modification of pig genes, and the tools for establishing pig models are now possible. Therefore, the establishment of pigs as genetic engineering tools shows a trend of rapid development.