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The Scientific Problems of Knockout Mice

written by: •edited by: Paul Arnold•updated: 8/23/2009

Since their creation in 1989, knockout mice have become invaluable tools for researchers tying to find out the functions of genes. But as good they are, there are limitations with using these genetically engineered animals.

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    Genetically Engineered Animals

    Knockout mice are genetically engineered animals that are created from modified embryonic stem cells. A gene being studied is knocked out or silenced and its function is inferred from the change in behaviour or condition of the animal when compared to normal mice. You can find out more about the process of creating knockout mice by clicking here.

    Humans and mice share many genes and physiological traits and knockout mice are powerful research tools that have helped with the study of such human diseases as cancer, arthritis, and Parkinson's. However, as good as they are, knockout mice have their limitations.

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    Problems of Knockout Mice

    The problems and limitations associated with knockout mice are as follows: -

    • About 15% of knockout mice are developmentally lethal which means that they don't grow to adulthood. This is a problem for scientists trying to find out how a gene being studied may cause problems for human health. Allied to this is the fact that some genes have different functions in the embryonic and adult states.
    • Sometimes there are developmental defects and the knockout mice will die whilst they are embryos. This means they are of no use as research tools.
    • Some of these lab animals will develop different phenotypic traits from their human counterparts. An example of this is the p53 knockout mouse model where the p53 gene has been silenced. Mutations of this gene have been implicated in more than half of all human cancers. However, in the knockout mice models the tumours will develop a different range of tumours. For example the mice will develop lymphomas and sarcomas whereas humans would develop epithelial-cell derived cancers. This makes comparative studies of gene function extraordinarily difficult. It cannot be assumed that the gene adopts identical functions in mouse and humans.
    • Some genes are difficult to knockout.

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    Mice Matter

    However, despite these limitations many researchers can't imagine carrying out medical research without knockout mice, and these lab animals have done so much to shed light on the pathogenesis of many different types of human diseases.