Molecular investigation of TBP allele length:

Reid, Suzanne J., Rees, Mark I., van Roon-Mom, Willeke M.C., Jones, Lesley ORCID: https://orcid.org/0000-0002-3007-4612, MacDonald, Marcy E., Sutherland, Greg, During, Matthew J., Faull, Richard L.M., Owen, Michael John ORCID: https://orcid.org/0000-0003-4798-0862, Dragunow, Mike and Snell, Russell G. 2003. Molecular investigation of TBP allele length:. Neurobiology of Disease 13 (1) , pp. 37-45. 10.1016/S0969-9961(03)00014-7

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Abstract

Recently, an inherited spinocerebellar ataxia (SCA17) has been attributed to polyglutamine coding expansions within the gene coding for human TATA-box binding protein (TBP). The normal repeat range is 25-42 units with patients having as few as 46 repeats. We undertook a TBP repeat length population study showing its relative stability, skewed distribution, and substantial population specific differences. To investigate the mechanism of neurodegeneration in SCA17 we have developed a cellular model expressing full-length TBP with a range of polyQ expansions. As has been found with other polyQ cellular models, insoluble intracellular inclusions form in a repeat-length-dependent manner. In addition, we have shown that the expanded TBP polyQ tract is able to interact with other overexpressed polyQ-containing proteins. Importantly, overexpression of expanded TBP results in increased Cre-dependent transcriptional activity. As TBP is required for transcription by all RNA polymerases, this may indicate a mechanism for aberrant polyQ gain of function.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG) Neuroscience and Mental Health Research Institute (NMHRI)
Subjects:	R Medicine > R Medicine (General)
Publisher:	Elsevier
ISSN:	0969-9961
Last Modified:	04 Mar 2023 03:02
URI:	https://orca.cardiff.ac.uk/id/eprint/82297

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