1. Development of blastocyst complementation technology without contributions to gametes and the brain.
- Author
-
Hashimoto H, Eto T, Yamamoto M, Yagoto M, Goto M, Kagawa T, Kojima K, Kawai K, Akimoto T, and Takahashi RI
- Subjects
- Animals, Brain physiology, Female, Germ Cells physiology, Japan, Male, Mice, Mice, Inbred ICR, Blastocyst cytology, Cell Differentiation physiology, Embryo Culture Techniques methods, Embryo Transfer methods, Mouse Embryonic Stem Cells cytology
- Abstract
In Japan, it is possible to generate chimeric animals from specified embryos by combining animal blastocysts with human pluripotent stem (PS) cells (animal-human PS chimera). However, the production of animal-human PS chimeras has been restricted because of ethical concerns, such as the development of human-like intelligence and formation of humanized gametes in the animals, owing to the contributions of human PS cells to the brain and reproductive organs. To solve these problems, we established a novel blastocyst complementation technology that does not contribute to the gametes or the brain. First, we established GFP-expressing mouse embryonic stem cells (G-mESCs) in which the Prdm14 and Otx2 genes were knocked out and generated chimeric mice by injecting them into PDX-1-deficient blastocysts. The results showed that the G-mESCs did not contribute to the formation of gametes and the brain. Therefore, in the PDX-1-deficient mice complemented by G-mESCs without the Prdm14 and Otx2 genes, the germline was not transmitted to the next generations. This approach could address concerns regarding the development of both human gametes and a human-like brain upon mouse blastocyst complementation using human stem cells.
- Published
- 2019
- Full Text
- View/download PDF