Choosing an animal model for the study of Huntington's disease

• Published in: Nature reviews. Neuroscience Vol. 14; no. 10; pp. 708 - 721
• Main Authors: Pouladi, Mahmoud A., Morton, A. Jennifer, Hayden, Michael R.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01-10-2013; Nature Publishing Group
• Subjects: 631/1647/334/2045; 631/378/1689/1558; 631/378/1934; 631/378/2611; Acids; Animal Genetics and Genomics; Animal models in research; Animals; Animals, Genetically Modified; Behavioral Sciences; Biological Techniques; Biomedicine; Clinical trials; Development and progression; Disease Models, Animal; Genetic aspects; Humans; Huntingtin Protein; Huntington Disease - classification; Huntington Disease - genetics; Huntington Disease - physiopathology; Huntington's chorea; Huntingtons disease; Mutation; Nerve Tissue Proteins - genetics; Neurobiology; Neurosciences; review-article; Species Specificity; Trinucleotide Repeats - genetics; Validation studies; Validity; United Kingdom; Singapore; Israel
• ISSN: 1471-003X; 1471-0048; 1469-3178
• DOI: 10.1038/nrn3570

Key Points
Animal models of Huntington's disease (HD), which have been established in species that range from worms, fruitflies, mice and rats to pigs, sheep and monkeys, have provided important insights into the pathogenesis of this disease.
Key distinguishing factors among animal models of HD are the genetic approach with which they were generated and the nature of the huntingtin (
HTT
) mutation that they carry.
The symptoms exhibited by each model largely reflect the genetic approach and transgene construct used to generate them.
Rodents are by far the most commonly used animals for modelling HD, with over 20 different models having been generated.
Different species of animals are better suited for modelling certain aspects of HD and for different applications. The choice of species and the particular model to use will therefore depend on the specific question of interest.
The goal of generating large animal models of HD should be pursued as certain challenges with regard to developing therapeutics for HD cannot be met in rodents and other small animals.
In this Review, Pouladi and colleagues critically examine the strengths and limitations of the currently available animal models of Huntington's disease. By doing so, they aim to facilitate animal model selection in future studies of this progressive neurodegenerative disorder.
Since the identification of the causative gene in Huntington's disease (HD), a number of animal models of this disorder have been developed. A frequently asked question is: which of these models most closely recapitulates the human disease? In this Review, we provide an overview of the currently available animal models of HD in the context of the clinical features of the disease. In doing so, we highlight their strengths and limitations for modelling specific symptoms of the disease. This should highlight the animal model that is best suited to address a particular question of interest and, ultimately, to expedite the discovery of treatments that will prevent or slow the progression of HD.