The long term goal for this work is to determine the molecular basis of Huntington's disease (HD). The basis for this progressive neurological disorder is an expanded CAG repeat in the Huntington gene that codes for a long polyglutamine repeat (11, 28, 51, 63, 69). The work proposed in this competitive renewal extends work completed during the first 2 years of funding during which the PI made a mouse with a 90 unit CAG repeat in the murine HD homolog (Hdh (CAG) 90). Recent work has shown the presence of Neuronal intranuclear inclusions (NIIs). The PI will also make mice with modifications of Hdh (CAG) 90 designed to enhance access of the polyglutamine-containing portion of the mutant protein to the nucleus. The PI will assess the role these modifications play in the formation of NIIs and the possible role NIIs play in causing abnormalities.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS034492-05
Application #
2892009
Study Section
Neurology C Study Section (NEUC)
Program Officer
Oliver, Eugene J
Project Start
1998-09-30
Project End
2002-07-31
Budget Start
1999-08-01
Budget End
2000-07-31
Support Year
5
Fiscal Year
1999
Total Cost
Indirect Cost
Name
University of Alabama Birmingham
Department
Biochemistry
Type
Schools of Medicine
DUNS #
004514360
City
Birmingham
State
AL
Country
United States
Zip Code
35294
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Dixon, Karen T; Cearley, Jamie A; Hunter, Jesse M et al. (2004) Mouse Huntington's disease homolog mRNA levels: variation and allele effects. Gene Expr 11:221-31
Jackson, Walker S; Tallaksen-Greene, Sara J; Albin, Roger L et al. (2003) Nucleocytoplasmic transport signals affect the age at onset of abnormalities in knock-in mice expressing polyglutamine within an ectopic protein context. Hum Mol Genet 12:1621-9
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Ordway, J M; Tallaksen-Greene, S; Gutekunst, C A et al. (1997) Ectopically expressed CAG repeats cause intranuclear inclusions and a progressive late onset neurological phenotype in the mouse. Cell 91:753-63
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