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Ultrastructural and molecular characterisation of the neuronal nucleus.

Slavik-Smith, E.; (2006) Ultrastructural and molecular characterisation of the neuronal nucleus. Doctoral thesis , University of London. Green open access

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Within the mammalian nucleus, many major cellular functions are performed including transcription, pre-mRNA splicing and ribosome assembly, all of which are important for successful gene expression, and, to achieve this, the nucleus has evolved as a highly organised, dynamic structure (Dundr and Misteli, 2001). In this study a complete ultrastructural and molecular investigation of the neuronal nucleus has been undertaken, characterising three subdomains in detail: speckles, the nucleolus, and the Cajal body. It has recently been established that several human neurodegenerative diseases are associated with changes in the organisation of the neuronal nucleus, and this is believed to be the principle cause of cellular dysfunction and resulting clinical symptoms. Many of these diseases and their associated nuclear pathology have successfully been reproduced in transgenic mouse models. In this study I have determined the detailed ultrastructural and molecular organisation of the nucleus of neurons within the striatum of the mouse brain and compared this to nuclei of striatal neurons in a transgenic mouse model of Huntington's disease and in a mutant mouse lacking the gene for the protein p80 coilin. In the HD mouse there is a dramatic reorganisation of the nucleus accompanied by the formation of a novel nuclear subdomain, the neuronal intranuclear inclusion (Nil), which is associated with the movement of the Cajal body from the nucleolus to the Nil. This occurs with a change in the molecular composition of the speckles and a major reorganisation in the structure of the nucleolus. In contrast, the p80 mutant mouse is characterised by major alterations in the distribution and molecular composition of the Cajal body. However, this is not similarly associated with dramatic changes in either the speckles or the nucleolus. These studies clearly establish novel and important changes in the organisation of the neuronal nucleus associated with the formation of the Nil in Huntington's disease.

Type: Thesis (Doctoral)
Title: Ultrastructural and molecular characterisation of the neuronal nucleus.
Identifier: PQ ETD:592410
Open access status: An open access version is available from UCL Discovery
Language: English
Additional information: Thesis digitised by ProQuest. Third party copyright material has been removed from the ethesis
UCL classification: UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Cell and Developmental Biology
URI: https://discovery.ucl.ac.uk/id/eprint/1445097
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