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A phenotypic characterisation of the HdhQ111 mouse model of Huntington’s disease

Yhnell, Emma 2015. A phenotypic characterisation of the HdhQ111 mouse model of Huntington’s disease. PhD Thesis, Cardiff University.
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Abstract

The work presented in this thesis focuses on a behavioural and histological characterisation of the HdhQ111 mouse model of Huntington’s disease (HD). Numerous mouse models of HD are currently available; however, before their use, each must be fully understood, validated and characterised, which will allow the most appropriate model to be used in scientific research. Chapter 1 provides a general introduction. Chapter 2 states the materials and methods used in this thesis. The work presented in Chapter 3 encompasses an extensive longitudinal immunohistological characterisation of the HdhQ111/+ mouse model, which includes immunohistochemical stains from animals at 3, 6, 9, 12, 15 and 18 months of age, to understand the development of the underlying neuropathology associated with this mouse model. Chapter 4 builds on the knowledge gained from the previous chapter to explore the longitudinal progression of motor symptoms associated with the HdhQ111/+ mouse model. In Chapter 5 a longitudinal operant battery was conducted to explore cognitive dysfunction in the HdhQ111/+ mouse model. Operant tests of motivation, attention and implicit learning were conducted longitudinally at 6, 12 and 18 months of age. Chapter 6 uses the knowledge gained from Chapter 5 to explore the effects of operant pre-training, at a young age, and the impact that this has on latter operant task performance and the development of the disease phenotype at an older age. To further understand the cognitive deficits observed in the HdhQ111/+ mouse model, Chapter 7 presents the creation, optimisation and utilisation of an operant delayed matching and delayed non-matching to position (DMTP/DNMTP) task, which could be used to test working memory and reversal learning in mouse models of neurological diseases including HD. Chapter 8 includes a general discussion of the work presented in this thesis. The studies presented within this thesis demonstrate the development of a clear neuropathological profile as well as significant motor and cognitive deficits in the HdhQ111 mouse model of Huntington’s disease. We can therefore conclude that the HdhQ111 mouse model is a valid mouse model for investigating the pathogenic mechanisms of Huntington's disease and for testing therapeutic interventions in HD.

Item Type: Thesis (PhD)
Status: Unpublished
Schools: Biosciences
Subjects: R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
Uncontrolled Keywords: Huntington's disease, Mouse model, Behaviour, Operant, Histology, Trinucleotide repeat
Funders: Medical Research Council
Date of First Compliant Deposit: 30 March 2016
Last Modified: 05 Dec 2019 11:27
URI: http://orca.cf.ac.uk/id/eprint/84348

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