Abstract

Recently, in collaboration with Dr. Huda Zohgbi (Baylor) we showed that spinocerebellar ataxia type 1 (SCA1) is due to an expansion of an unstable CAG repeat within the ataxin-1 gene on human chromosome 6p. The goal of the work proposed in this project is to study the biology of the ataxin-1 gene in the mouse. This will be achieved by: 1) Examining the tissue and developmental pattern of ataxin-1 expression in the mouse using in situ hybridization, and 2) The development and characterization of a mouse model of SCA1. Our laboratory has considerable expertise in the use of transgenic mice to study cerebellar Purkinje cells (a major site of cellular degeneration in individuals affected with SCA1). Thus, we are positioned to determine if transgenic mice expressing an expanded allele of the SCA1 gene are a suitable model of, 1) the human disease, and 2) a genetically unstable CAG repeat. A mouse model of SCA1 will provide valuable information concerning the function of ataxin-1 gene in normal cerebellar physiology, the pathologenesis of SCA1. Transgenic mice, carrying human ataxin-1 genes with various CAG repeat configurations, will also be examined as possible models for unstable (intergenerational) trinucleotide repeats.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Program Projects (P01)
Project #
5P01NS033718-03
Application #
6243820
Study Section
Project Start
1997-01-01
Project End
1997-12-31
Budget Start
1996-10-01
Budget End
1997-09-30
Support Year
3
Fiscal Year
1997
Total Cost
Indirect Cost

  Institution

Name
University of Minnesota Twin Cities
Department
Type
DUNS #
168559177
City
Minneapolis
State
MN
Country
United States
Zip Code
55455

  Publications

Sidtis, John J; Strother, Stephen C; Groshong, Ansam et al. (2010) Longitudinal cerebral blood flow changes during speech in hereditary ataxia. Brain Lang 114:43-51
Sidtis, John J; Gomez, Christopher; Groshong, Ansam et al. (2006) Mapping cerebral blood flow during speech production in hereditary ataxia. Neuroimage 31:246-54
Arnold, J B; Liow, J S; Schaper, K A et al. (2001) Qualitative and quantitative evaluation of six algorithms for correcting intensity nonuniformity effects. Neuroimage 13:931-43
Muley, S A; Strother, S C; Ashe, J et al. (2001) Effects of changes in experimental design on PET studies of isometric force. Neuroimage 13:185-95
Liow, J S; Zhou, L (2000) Evaluating performance of reconstruction algorithms for 3-D [15O] water PET using subtraction analysis. IEEE Trans Med Imaging 19:522-31
Sidtis, J J (2000) From chronograph to functional image: what's next? Brain Cogn 42:75-7
Frutiger, S A; Strother, S C; Anderson, J R et al. (2000) Multivariate predictive relationship between kinematic and functional activation patterns in a PET study of visuomotor learning. Neuroimage 12:515-27
Day, J W; Schut, L J; Moseley, M L et al. (2000) Spinocerebellar ataxia type 8: clinical features in a large family. Neurology 55:649-57
Moseley, M L; Schut, L J; Bird, T D et al. (2000) SCA8 CTG repeat: en masse contractions in sperm and intergenerational sequence changes may play a role in reduced penetrance. Hum Mol Genet 9:2125-30
Clark, H B; Orr, H T (2000) Spinocerebellar ataxia type 1--modeling the pathogenesis of a polyglutamine neurodegenerative disorder in transgenic mice. J Neuropathol Exp Neurol 59:265-70

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