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Beyond the Rat Models of Human Neurodegenerative Disorders

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Abstract

The rat is a model of choice in biomedical research for over a century. Currently, the rat presents the best “functionally” characterized mammalian model system. Despite this fact, the transgenic rats have lagged behind the transgenic mice as an experimental model of human neurodegenerative disorders. The number of transgenic rat models recapitulating key pathological hallmarks of Alzheimer’s disease, Huntington’s disease, amyotrophic lateral sclerosis, or human tauopathies is still limited. The reason is that the transgenic rats remain more difficult to produce than transgenic mice. The gene targeting technology is not yet established in rats due to the lack of truly totipotent embryonic stem cells and cloning technology. This extremely powerful technique has given the mouse a clear advantage over the rat in generation of new transgenic models. Despite these limitations, transgenic rats have greatly expanded the range of potential experimental approaches. The large size of rats permits intrathecal administration of drugs, stem cell transplantation, serial sampling of the cerebrospinal fluid, microsurgical techniques, in vivo nerve recordings, and neuroimaging procedures. Moreover, the rat is routinely employed to demonstrate therapeutic efficacy and to assess toxicity of novel therapeutic compounds in drug development. Here we suggest that the rat constitutes a slightly underestimated but perspective animal model well-suited for understanding the mechanisms and pathways underlying the human neurodegenerative disorders.

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Acknowledgment

This work was supported by research grants APVV 0631-07 and LPP-0363-06.

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Authors and Affiliations

  1. Institute of Neuroimmunology, Slovak Academy of Sciences, AD Centre, Dubravska cesta 9, 845 10, Bratislava, Slovak Republic

    Ondrej Bugos, Mangesh Bhide & Norbert Zilka

  2. Axon-Neuroscience GmbH, Rennweg 95b, 1030, Vienna, Austria

    Norbert Zilka

  3. Laboratory of Biomedical Microbiology and Immunology, University of Veterinary Medicine, Komenskeho 73, 041 81, Kosice, Slovak Republic

    Mangesh Bhide

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  1. Ondrej Bugos
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Correspondence to Norbert Zilka.

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Bugos, O., Bhide, M. & Zilka, N. Beyond the Rat Models of Human Neurodegenerative Disorders. Cell Mol Neurobiol 29, 859–869 (2009). https://doi.org/10.1007/s10571-009-9367-5

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