Juvenile Huntington’s disease and mouse models of Huntington’s disease

Gillian P. Bates and Ben Woodman

in Juvenile Huntington's Disease

Published on behalf of Oxford University Press

Published in print January 2009 | ISBN: 9780199236121
Published online November 2012 | e-ISBN: 9780191753213 | DOI:
Juvenile Huntington’s disease and mouse models of Huntington’s disease

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The isolation of the Huntington’s disease (HD) gene in 1993 made it feasible to generate models of HD in any of the organisms amenable to genetic manipulation including yeast, Caenorhabditis elegans, Drosophila melanogaster, mouse, and rat. The ability to generate mammalian models has been of fundamental importance to ensure that discoveries made in single-celled organisms and invertebrates are applicable in the context of mammalian neural networks and physiology. Although both mouse and rat models have been generated, the ease with which the mouse genome can be manipulated has made this the system of choice. Mouse and rat models overcome the limitations of studying post-mortem HD brain material as they allow the onset and progression of phenotypes to be tracked, enabling the primary events in the pathogenesis of the disease to be unravelled. They can also be used for preclinical screening and are likely to be the system that provides the filter to determine which compounds are taken forward for clinical evaluation. Mouse lines that carry specialized modifications have been generated in order to dissect specific aspects of the pathogenesis of HD, and the wide range of genetically modified mouse strains available allows for the validation of therapeutic targets by conducting genetic crosses between HD mouse lines and strains of interest.

This chapter begins by summarizing the approaches that can be used to generate rodent models of disease. The limitations in generating models of a mid-life onset disease and the means by which these have been overcome are discussed. After outlining some of the major features of the HD rodent models, the more specialized approaches that can be used to manipulate the mouse genome and how these have been used to dissect aspects of HD pathogenesis are presented. The chapter concludes by describing some of the insights into HD pathogenesis that have been gained through the analysis of HD mouse models and their relationship to juvenile HD.

Chapter.  5155 words. 

Subjects: Neurology

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