A review of current large-scale mouse knockout efforts

Area of Science:

• Genomics and Molecular Biology
• Animal Models
• Functional Genomics

Background:

• The post-human genome project era necessitates efficient gene function analysis.
• Knockout mouse models are crucial for understanding gene function and developing disease therapies.
• Gene trapping and gene targeting are established methods for creating knockout mice from embryonic stem cells.

Purpose of the Study:

• To review advancements in gene trapping and targeting techniques for creating knockout mouse models.
• To highlight the role of large-scale initiatives in generating comprehensive knockout mouse resources.
• To discuss the evolution of methods towards high-throughput and conditional gene manipulation.

Main Methods:

• Gene targeting: precise gene modification.
• Gene trapping: random, sequence-tagged insertional mutagenesis.
• Utilizing embryonic stem (ES) cells for genetic modification.
• Development of new tools, including transposons, for gene trapping.

Main Results:

• Significant progress in both gene targeting and gene trapping technologies over two decades.
• Establishment of major projects like KOMP and IGTC to create extensive knockout mouse resources.
• Emergence of the International Knockout Mouse Consortium (IKMC) for global gene knockout efforts.

Conclusions:

• New tools and collaborative projects are enhancing the efficiency and scope of knockout mouse generation.
• Systematic knockout of all mouse genes is underway, providing invaluable resources for functional genomics.
• These efforts are critical for advancing biological research and therapeutic development.