Evolution, Applications, and Perspectives of Technologies for Genetically Engineered Mouse Generation
10.12300/j.issn.1674-5817.2026.028
- VernacularTitle:基因工程小鼠构建技术的演进、应用与展望
- Author:
Jianfeng WU
1
;
Zhiqiang SHAO
1
;
Ying HE
1
;
Suqin WU
1
Author Information
1. Xiamen University Laboratory Animal Center, Xiamen 361102, China
- Publication Type:Journal Article
- Keywords:
Genetically engineered mice;
Gene targeting technology;
Random mutagenesis models;
CRISPR/Cas system
- From:
Laboratory Animal and Comparative Medicine
2026;46(5):759-770
- CountryChina
- Language:Chinese
-
Abstract:
Genetically engineered mice are important tools for elucidating gene function and disease mechanisms and for advancing drug development. With the growing demand in biomedical research for complex genetic modifications, rapid model generation, and high-throughput functional analysis, technologies for generating genetically engineered mice continue to evolve. This review systematically summarizes the evolution and applications of these technologies, with a focus on conventional approaches, including early transgenic technologies and embryonic stem cell (ESC)-based homologous recombination for gene targeting, as well as the use of random mutagenesis approaches, such as N-ethyl-N-nitrosourea (ENU) mutagenesis and transposon insertion, in forward genetic screening. It further discusses the principles and characteristics of programmable nucleases, including zinc finger nucleases, transcription activator-like effector nucleases, and CRISPR/Cas systems, as well as their applications in generating genetically engineered mice. With advances in genome editing, Cas9-derived systems, base editing, prime editing, and RNA editing further improve editing precision, expand the repertoire of genetic modifications and precise regulatory approaches, and provide additional options for generating genetically engineered mice. This review also compares the advantages, limitations, and suitability of different technologies for specific applications and summarizes quality-control strategies addressing practical issues that may affect model reliability, including off-target effects, mosaicism, genetic background, and genetic stability. Finally, future directions in technologies for generating genetically engineered mice are discussed to inform the generation and application of related models.