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Nonmammalian Models of Huntington’s Disease

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Huntington’s Disease

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1780))

Abstract

Flies, worms, yeast and more recently zebra fish have all been engineered to express expanded polyglutamine repeat versions of Huntingtin with various resulting pathologies including early death, neurodegeneration, and loss of motor function. Each of these models present particular features that make it useful in studying the mechanisms of polyglutamine pathology. However, one particular unbiased readout of mHTT pathology is functional loss of motor control. Loss of motor control is prominent in patients, but it remains unresolved whether pathogenic symptoms in patients result from overt degeneration and loss of neurons or from malfunctioning of surviving neurons as the pathogenic insult builds up. This is why a functional assay such as motor control can be uniquely powerful in revealing early as well as late neurological deficits and does not rely on assumptions such as that the level of inclusions or the degree of neuronal loss can be equated with the level of pathology. Drosophila is well suited for such assays because it contains a functioning nervous system with many parallels to the human condition. In addition, the ability to readily express mHTT transgenes in different tissues and subsets of neurons allows one the possibility of isolating a particular effect to a subset of neurons where one can correlate subcellular events in response to mHTT challenge with pathology at both the cellular and organismal levels. Here we describe methods to monitor the degree of motor function disruption in Drosophila models of HD and we include a brief summary of other nonmammalian models of HD and discussion of their unique strengths.

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Acknowledgements

Support was provided by HD CARE, R01-NS-045283.

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Authors and Affiliations

  1. Department of Developmental and Cell Biology, University of California, Irvine, Irvine, 92697, CA, USA

    Anjalika Chongtham, Brett Barbaro, Tomas Filip, Adeela Syed, Weijian Huang, Marianne R. Smith & J. Lawrence Marsh

  2. The Scripps Research Institute, La Jolla, CA, USA

    Brett Barbaro

  3. Biology Centre Czech Acad. Sci., Ceske Budejovice, Czech Republic

    Tomas Filip

  4. University Advancement, UC Irvine, Irvine, CA, USA

    Marianne R. Smith

Authors
  1. Anjalika Chongtham
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  2. Brett Barbaro
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  3. Tomas Filip
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  4. Adeela Syed
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  5. Weijian Huang
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  6. Marianne R. Smith
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  7. J. Lawrence Marsh
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Correspondence to J. Lawrence Marsh .

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Editors and Affiliations

  1. Brain Repair Group, Cardiff University, Cardiff, United Kingdom

    Sophie V. Precious

  2. Brain Repair Group, Cardiff University, Cardiff, United Kingdom

    Anne E. Rosser

  3. Brain Repair Group, Cardiff University, Cardiff, United Kingdom

    Stephen B. Dunnett

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Chongtham, A. et al. (2018). Nonmammalian Models of Huntington’s Disease. In: Precious, S., Rosser, A., Dunnett, S. (eds) Huntington’s Disease. Methods in Molecular Biology, vol 1780. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-7825-0_5

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  • DOI: https://doi.org/10.1007/978-1-4939-7825-0_5

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  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-7824-3

  • Online ISBN: 978-1-4939-7825-0

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