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Updated: Jul 11, 2026
Somatic Genome-Engineered Mouse Models Using In Vivo Microinjection and Electroporation
Published on: May 5, 2023
Gene trap mutagenesis in mice: new perspectives and tools in cancer research
Ken-ichi Yamamura1, Kimi Araki
1Division of Developmental Genetics, Institute of Molecular Embryology and Genetics, Kumamoto University, 2-2-1 Honjo, Kumamoto 860-0811, Japan. yamamura@gpo.kumamoto-u.ac.jp
Abstract:
The complete human DNA sequence of the human genome was published in 2004 and we entered the postgenomic era. However, many studies showed that gene function is much more complex than we expected, and that mutation of disease genes does not give any clue for molecular mechanisms for disease development. Since the first report on gene knockout mice in 1989, knockout mice have been shown to be a powerful tool for functional genomics and for the dissection of developmental processes in human diseases. In accordance with this successful application of knockout mice, three major mouse knockout programs are now underway worldwide, to mutate all protein-encoding genes in mouse embryonic stem cells using a combination of gene trapping and gene targeting. We developed the exchangeable gene trap method suitable for large scale mutagenesis in mice. In this method we can produce null mutation and post-insertional modification, enabling replacement of the marker gene with a gene of interest and conditional knockout. We herein discuss the effect of this gene-driven type approach for cancer research, especially for finding the genes that are related to cancer, but are paid little attention in hypothesis-driven cancer research.
Insights
Gene knockout mice are crucial for understanding complex gene functions and diseases. A new exchangeable gene trap method facilitates large-scale mouse mutagenesis for cancer research.
Area of Science:
- Genomics
- Molecular Biology
- Developmental Biology
Background:
- The postgenomic era, following the human genome sequence publication in 2004, revealed gene function complexity beyond initial expectations.
- Gene mutations alone often fail to elucidate disease molecular mechanisms.
- Gene knockout mice, since 1989, have become indispensable tools for functional genomics and studying human diseases.
Purpose of the Study:
- To introduce an exchangeable gene trap method for large-scale mouse mutagenesis.
- To discuss the application of this gene-driven approach in cancer research, particularly for identifying understudied cancer-related genes.
Main Methods:
- Development of an exchangeable gene trap system for mouse embryonic stem cells.
- Utilizing gene trapping and gene targeting for large-scale mutagenesis.
- Enabling null mutation, post-insertional modification, and conditional knockout.
Main Results:
- The developed method is suitable for high-throughput mutagenesis in mice.
- It allows for the creation of various mutation types, including conditional knockouts.
- Facilitates the identification of novel cancer-related genes through a gene-driven approach.
Conclusions:
- The exchangeable gene trap method offers a powerful tool for functional genomics and large-scale mutagenesis.
- This gene-driven strategy can uncover genes relevant to cancer that may be missed by hypothesis-driven research.
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