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A Knockout Blow for Knockout Mice?

written by: •edited by: Paul Arnold•updated: 12/4/2009

Knockout mice have taken the lab limelight for a number of years and contributed to great swathes of knowledge about human diseases. But they could be pushed aside by the creation of a knockout lab rat without a functioning immune system.

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    Knockout Mice

    Human and mouse physiology and genetics are quite similar and these facts have contributed to the employment of knockout mice to boost our understanding of several disease processes such as cancers and heart disease. Knockout mice are powerful tools that have been genetically engineered to turn off the expression of a gene under study. In this way its function can be inferred by comparing the behaviour or condition of the knockout mouse with a normal mouse. However, knockout mice have some limitations which make the use of lab rats a more attractive option. And rats are more closely related to humans than mice. For example the mouse heart beats 5-10 times faster whilst the heart of a rat is more in line with our own heart. We also share similar liver enzymes to rats and so eradicate toxins in a similar way. This makes rats a better model for studying the toxicity of potential therapeutics.

    Rats are also more intelligent than mice and knockout rats could be used for the study of behaviours and neurological conditions.

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    Knockout Rats

    So why have we been using knockout mice over rats? Rats have lagged behind because the technology was difficult and it wasn't economically viable, though that is not the case now. The first knockout rats started to appear in 2008. The gene knockouts can be achieved by using transposons and retrotransposons which are mobile pieces of DNA which can induce mutations in a genome. And zinc finger nucleases are DNA-binding proteins that can create double-stranded breaks at specific locations within DNA. A cell will then repair itself and the inaccuracy of this process can create targeted mutations.

    And in 2009 scientists figured out a way of silencing the rat immune system. The immune system of a lab animal has to be switched off otherwise it can affect and complicate test results.

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    Genetically Engineered Lab Rats

    A team of scientists from Transposagen Biopharmaceuticals of Lexington, Kentucky have created a rat that has no functioning immune system, a condition that resembles combined immune deficiency disease in humans. It's therefore been called a "SCID rat" by the team.

    The researchers achieved their aims by switching off key immune system genes by mutating embryonic DNA. It's expected that in the near future the knockout rats will be used for immunology research, cancer research, and transplant studies.

    All this combined with the fact they can be produced cost-effectively may mean that the knockout rat will soon become a scientist's best friend in the laboratory.

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