Abstract

The long term objective of the proposed work is to isolate and characterize the gene for the neurodegenerative genetic disorder spinocerebellar ataxia (SCA). The approach will be to first identify DNA markers that will enable the precise chromosomal localization of the SCA gene by linkage using two very large SCA families and the CEPH panel of reference families. The next step will be to use DNA markers that are close to the SCA gene by DNA cloning. Once the gene is isolated, it will be possible to determine the alteration that results in SCA. This will provide important insights into the development of this cerebellar degenerative disease and may also provide clues into the genetic basis of other neuronal degenerative diseases.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS022920-06
Application #
2264649
Study Section
Genome Study Section (GNM)
Project Start
1986-08-01
Project End
1996-02-28
Budget Start
1994-03-01
Budget End
1995-02-28
Support Year
6
Fiscal Year
1994
Total Cost
Indirect Cost

  Institution

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

  Publications

Rubinsztein, David C; Orr, Harry T (2016) Diminishing return for mechanistic therapeutics with neurodegenerative disease duration?: There may be a point in the course of a neurodegenerative condition where therapeutics targeting disease-causing mechanisms are futile. Bioessays 38:977-80
Nelson, David L; Orr, Harry T; Warren, Stephen T (2013) The unstable repeats--three evolving faces of neurological disease. Neuron 77:825-43
Ebner, Blake A; Ingram, Melissa A; Barnes, Justin A et al. (2013) Purkinje cell ataxin-1 modulates climbing fiber synaptic input in developing and adult mouse cerebellum. J Neurosci 33:5806-20
Orr, Harry T (2012) Cell biology of spinocerebellar ataxia. J Cell Biol 197:167-77
Ingram, Melissa A C; Orr, Harry T; Clark, H Brent (2012) Genetically engineered mouse models of the trinucleotide-repeat spinocerebellar ataxias. Brain Res Bull 88:33-42
Orr, Harry T (2012) Polyglutamine neurodegeneration: expanded glutamines enhance native functions. Curr Opin Genet Dev 22:251-5
Fryer, John D; Yu, Peng; Kang, Hyojin et al. (2011) Exercise and genetic rescue of SCA1 via the transcriptional repressor Capicua. Science 334:690-3
Gehrking, Kristin M; Andresen, J Michael; Duvick, Lisa et al. (2011) Partial loss of Tip60 slows mid-stage neurodegeneration in a spinocerebellar ataxia type 1 (SCA1) mouse model. Hum Mol Genet 20:2204-12
Oz, Gülin; Vollmers, Manda L; Nelson, Christopher D et al. (2011) In vivo monitoring of recovery from neurodegeneration in conditional transgenic SCA1 mice. Exp Neurol 232:290-8
Barnes, Justin A; Ebner, Blake A; Duvick, Lisa A et al. (2011) Abnormalities in the climbing fiber-Purkinje cell circuitry contribute to neuronal dysfunction in ATXN1[82Q] mice. J Neurosci 31:12778-89

Showing the most recent 10 out of 62 publications