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A Genetically Engineered Mouse Model of Sporadic Colorectal Cancer
Published on: July 6, 2017
Conditional knockout mouse models of cancer
1Genetics of Development and Disease Branch, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892.
Abstract:
In 2007, three scientists, Drs. Mario R. Capecchi, Martin J. Evans, and Oliver Smithies, received the Nobel Prize in Physiology or Medicine for their contributions of introducing specific gene modifications into mice. This technology, commonly referred to as gene targeting or knockout, has proven to be a powerful means for precisely manipulating the mammalian genome and has generated great impacts on virtually all phases of mammalian biology and basic biomedical research. Of note, germline mutations of many genes, especially tumor suppressors, often result in lethality during embryonic development or at developmental stages before tumor formation. This obstacle has been effectively overcome by the use of conditional knockout technology in conjunction with Cre-LoxP- or Flp-Frt-mediated temporal and/or spatial systems to generate genetic switches for precise DNA recombination. Currently, numerous conditional knockout mouse models have been successfully generated and applied in studying tumor initiation, progression, and metastasis. This review summarizes some conditional mutant mouse models that are widely used in cancer research and our understanding of the possible mechanisms underlying tumorigenesis.
Insights
Gene targeting technology allows precise genome manipulation in mice, advancing biomedical research. Conditional knockout models overcome developmental hurdles, aiding cancer research into tumor initiation and progression.
Area of Science:
- Genetics
- Genomics
- Mammalian Biology
Background:
- Gene targeting, or knockout technology, enables precise manipulation of the mammalian genome.
- Nobel Prize-winning research in 2007 recognized gene modification techniques in mice.
- Germline mutations in tumor suppressors can cause embryonic lethality, hindering cancer research.
Purpose of the Study:
- To review conditional knockout mouse models widely used in cancer research.
- To explore their application in understanding tumorigenesis mechanisms.
- To highlight advancements in studying tumor initiation, progression, and metastasis.
Main Methods:
- Utilizing conditional knockout technology with Cre-LoxP or Flp-Frt systems.
- Generating genetic switches for temporal and/or spatial DNA recombination.
- Developing and applying conditional mutant mouse models.
Main Results:
- Conditional knockout technology effectively overcomes embryonic lethality associated with germline mutations.
- Numerous conditional knockout mouse models have been successfully generated.
- These models are instrumental in studying various stages of cancer development.
Conclusions:
- Conditional knockout mouse models are crucial tools in cancer research.
- They provide insights into the mechanisms underlying tumor initiation, progression, and metastasis.
- This technology significantly advances our understanding of mammalian biology and biomedical research.
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