Molecular investigation of TBP allele length:

Suzanne J. Reid; 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

Neurobiology of Disease (Jun 2003)

Molecular investigation of TBP allele length:

Suzanne J. Reid,
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

Suzanne J. Reid: Department of Molecular Medicine, University of Auckland, Private Bag 92019, Auckland, New Zealand; Department of Anatomy with Radiology, University of Auckland, Private Bag 92019, Auckland, New Zealand; Department of Medical Genetics, University of Wales College of Medicine, Heath Park, Cardiff, UK; Molecular Neurogenetics Unit, Massachusetts General Hospital, Charlestown, MA, USA; Department of Psychological Medicine, University of Wales College of Medicine, Heath Park, Cardiff, UK; Department of Pharmacology, University of Auckland, Private Bag 92019, Auckland, New Zealand
Mark I. Rees: Department of Molecular Medicine, University of Auckland, Private Bag 92019, Auckland, New Zealand; Department of Anatomy with Radiology, University of Auckland, Private Bag 92019, Auckland, New Zealand; Department of Medical Genetics, University of Wales College of Medicine, Heath Park, Cardiff, UK; Molecular Neurogenetics Unit, Massachusetts General Hospital, Charlestown, MA, USA; Department of Psychological Medicine, University of Wales College of Medicine, Heath Park, Cardiff, UK; Department of Pharmacology, University of Auckland, Private Bag 92019, Auckland, New Zealand
Willeke M.C. van Roon-Mom: Department of Molecular Medicine, University of Auckland, Private Bag 92019, Auckland, New Zealand; Department of Anatomy with Radiology, University of Auckland, Private Bag 92019, Auckland, New Zealand; Department of Medical Genetics, University of Wales College of Medicine, Heath Park, Cardiff, UK; Molecular Neurogenetics Unit, Massachusetts General Hospital, Charlestown, MA, USA; Department of Psychological Medicine, University of Wales College of Medicine, Heath Park, Cardiff, UK; Department of Pharmacology, University of Auckland, Private Bag 92019, Auckland, New Zealand
A.Lesley Jones: Department of Molecular Medicine, University of Auckland, Private Bag 92019, Auckland, New Zealand; Department of Anatomy with Radiology, University of Auckland, Private Bag 92019, Auckland, New Zealand; Department of Medical Genetics, University of Wales College of Medicine, Heath Park, Cardiff, UK; Molecular Neurogenetics Unit, Massachusetts General Hospital, Charlestown, MA, USA; Department of Psychological Medicine, University of Wales College of Medicine, Heath Park, Cardiff, UK; Department of Pharmacology, University of Auckland, Private Bag 92019, Auckland, New Zealand
Marcy E. MacDonald: Department of Molecular Medicine, University of Auckland, Private Bag 92019, Auckland, New Zealand; Department of Anatomy with Radiology, University of Auckland, Private Bag 92019, Auckland, New Zealand; Department of Medical Genetics, University of Wales College of Medicine, Heath Park, Cardiff, UK; Molecular Neurogenetics Unit, Massachusetts General Hospital, Charlestown, MA, USA; Department of Psychological Medicine, University of Wales College of Medicine, Heath Park, Cardiff, UK; Department of Pharmacology, University of Auckland, Private Bag 92019, Auckland, New Zealand
Greg Sutherland: Department of Molecular Medicine, University of Auckland, Private Bag 92019, Auckland, New Zealand; Department of Anatomy with Radiology, University of Auckland, Private Bag 92019, Auckland, New Zealand; Department of Medical Genetics, University of Wales College of Medicine, Heath Park, Cardiff, UK; Molecular Neurogenetics Unit, Massachusetts General Hospital, Charlestown, MA, USA; Department of Psychological Medicine, University of Wales College of Medicine, Heath Park, Cardiff, UK; Department of Pharmacology, University of Auckland, Private Bag 92019, Auckland, New Zealand
Matthew J. During: Department of Molecular Medicine, University of Auckland, Private Bag 92019, Auckland, New Zealand; Department of Anatomy with Radiology, University of Auckland, Private Bag 92019, Auckland, New Zealand; Department of Medical Genetics, University of Wales College of Medicine, Heath Park, Cardiff, UK; Molecular Neurogenetics Unit, Massachusetts General Hospital, Charlestown, MA, USA; Department of Psychological Medicine, University of Wales College of Medicine, Heath Park, Cardiff, UK; Department of Pharmacology, University of Auckland, Private Bag 92019, Auckland, New Zealand
Richard L.M. Faull: Department of Molecular Medicine, University of Auckland, Private Bag 92019, Auckland, New Zealand; Department of Anatomy with Radiology, University of Auckland, Private Bag 92019, Auckland, New Zealand; Department of Medical Genetics, University of Wales College of Medicine, Heath Park, Cardiff, UK; Molecular Neurogenetics Unit, Massachusetts General Hospital, Charlestown, MA, USA; Department of Psychological Medicine, University of Wales College of Medicine, Heath Park, Cardiff, UK; Department of Pharmacology, University of Auckland, Private Bag 92019, Auckland, New Zealand
Michael J. Owen: Department of Molecular Medicine, University of Auckland, Private Bag 92019, Auckland, New Zealand; Department of Anatomy with Radiology, University of Auckland, Private Bag 92019, Auckland, New Zealand; Department of Medical Genetics, University of Wales College of Medicine, Heath Park, Cardiff, UK; Molecular Neurogenetics Unit, Massachusetts General Hospital, Charlestown, MA, USA; Department of Psychological Medicine, University of Wales College of Medicine, Heath Park, Cardiff, UK; Department of Pharmacology, University of Auckland, Private Bag 92019, Auckland, New Zealand
Mike Dragunow: Department of Molecular Medicine, University of Auckland, Private Bag 92019, Auckland, New Zealand; Department of Anatomy with Radiology, University of Auckland, Private Bag 92019, Auckland, New Zealand; Department of Medical Genetics, University of Wales College of Medicine, Heath Park, Cardiff, UK; Molecular Neurogenetics Unit, Massachusetts General Hospital, Charlestown, MA, USA; Department of Psychological Medicine, University of Wales College of Medicine, Heath Park, Cardiff, UK; Department of Pharmacology, University of Auckland, Private Bag 92019, Auckland, New Zealand
Russell G. Snell: Department of Molecular Medicine, University of Auckland, Private Bag 92019, Auckland, New Zealand; Department of Anatomy with Radiology, University of Auckland, Private Bag 92019, Auckland, New Zealand; Department of Medical Genetics, University of Wales College of Medicine, Heath Park, Cardiff, UK; Molecular Neurogenetics Unit, Massachusetts General Hospital, Charlestown, MA, USA; Department of Psychological Medicine, University of Wales College of Medicine, Heath Park, Cardiff, UK; Department of Pharmacology, University of Auckland, Private Bag 92019, Auckland, New Zealand

Journal volume & issue: Vol. 13, no. 1
pp. 37 – 45

Abstract

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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.

Published in Neurobiology of Disease

ISSN: 0969-9961 (Print); 1095-953X (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Internal medicine: Neurosciences. Biological psychiatry. Neuropsychiatry
Website: https://www.journals.elsevier.com/neurobiology-of-disease

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