Diploid embryo complementation of embryonic stem cells efficiently generates a homozygous Gjb2 mutant deaf mouse model

Our work demonstrates that generating all ESC-derived mice via diploid embryo complementation is more efficient and feasible than the tetraploid approach. The broad application of this method will significantly accelerate the construction of disease models and xenogeneic chimeras using stem cell technology. Besides, our results indicate that the cell fate plasticity of eight-cell embryos is both flexible and variable. This plasticity is influenced by material exchange, through which embryonic stem cells transmit information, similar to the transmission of information from the second polar body. The efficient generation of Gjb235delG/35delG mice via diploid complementation will accelerate the understanding of pathogenic mechanisms and the investigation of therapeutic effects for hereditary deafness. Additionally, other disease models with GJB2 pathogenic mutations (235delC, V27I, R75W, etc.) can also be efficiently produced using this method for pre-clinical research