https://bio.nikkeibp.co.jp/atcl/news/p1/25/03/04/13034/
The National Agriculture and Food Research Organization (NARO) is developing immunodeficient pigs for the purpose of reproducing human pathological models and producing organs for transplantation into humans. Recently, the organization has miniaturized immunodeficient pigs to make them easier to use in experiments.
Since 2012, NARO develops immunodeficient pigs in collaboration with RIKEN and Primetech. The pigs are genetically modified to lack the gene that codes for the gamma chain of the interleukin 2 receptor (IL2RG). Pigs have XY sex chromosomes, just like humans, and the IL2RG gene is present on the X chromosome. IL2RG is a component of many interleukin receptors, and when IL2RG is missing, these are not produced normally, so immunodeficient pigs lack the thymus, lymph nodes, T cells, and natural killer (NK) cells, and their immune systems do not function because they do not produce antibodies. In fact, in cases where bone marrow cells from unrelated pigs, human stem cells, and human-derived cancer cells were transplanted, the cells were not rejected by the immune system and engrafted.
However, the size of conventional immunodeficient pigs is an issue. Experiments using immunodeficient pigs require sterile equipment to protect the pigs from infection, and if the pigs are too large, it becomes difficult to put them into the equipment.
Thus, a team at NARO created a miniature immunodeficient pig by crossbreeding a miniature pig developed by knocking out the growth hormone receptor (GHR) gene of a normal pig using genome editing with an immunodeficient pig with IL2RG knocked out. Immuclodeficient pigs that do not have normal GHR alleles are expected to be about 50% smaller than conventional immunodeficient pigs. These miniature immunodeficient pigs could also be used in research that requires long-term experiments, such as transplanting human cancer cells into pigs to verify the effectiveness of therapeutic drugs and investigating the tumorigenicity of regenerative medicine products.
