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
|
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: | Schools > Medicine Research Institutes & Centres > MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG) Research Institutes & Centres > Neuroscience and Mental Health Research Institute (NMHII) |
| 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 |
Citation Data
Cited 26 times in Scopus. View in Scopus. Powered By Scopus® Data
Actions (repository staff only)
 |
Edit Item |
Altmetric
Altmetric