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. 2003 Jun;13(1):37-45.
doi: 10.1016/s0969-9961(03)00014-7.

Molecular investigation of TBP allele length: a SCA17 cellular model and population study

Suzanne J Reid  1 , Mark I Rees, Willeke M C van Roon-Mom, A Lesley Jones, Marcy E MacDonald, Greg Sutherland, Matthew J During, Richard L M Faull, Michael J Owen, Mike Dragunow, Russell G Snell
Affiliations

Molecular investigation of TBP allele length: a SCA17 cellular model and population study

Suzanne J Reid et al. Neurobiol Dis. 2003 Jun.

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.

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