The long term objective of this study is to elucidate the molecular pathology of Huntington's disease (HD). The genetic basis for this progressive neurodegenerative disorder is an expanded CAG repeat in the coding region of the huntingtin gene. Towards this long term goal we will expand the CAG repeat of the endogenous huntingtin gene in murine embryonic stem (ES) cells using a gene targeting strategy that facilitates the introduction of several different lengths of repeat into a predetermined location in the mouse genome. From these ES cells we will produce mice with different lengths of CAG repeat (100-400 CAGs). Using the mouse with the longest repeat compatible with survival, we will study the effect of a long repeat on several factors that may be relevant to HD: 1) the length of the repeat in selected tissues, 2) the level of huntingtin mRNA and protein in selected tissues, and 3) the phenotype of the mouse. Although this work is not dependent on obtaining a mouse with a neurodegenerative phentotype, it may produce a mouse model for HD. A mouse with symptoms of HD would serve as a tool to study the molecular basis of HD pathology and as a source of experimental subjects for the discovery and assessment of therapies.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS034492-03
Application #
2431285
Study Section
Neurology C Study Section (NEUC)
Program Officer
Oliver, Eugene J
Project Start
1995-08-01
Project End
1998-05-31
Budget Start
1997-06-01
Budget End
1998-05-31
Support Year
3
Fiscal Year
1997
Total Cost
Indirect Cost
Name
University of Alabama Birmingham
Department
Biochemistry
Type
Schools of Dentistry
DUNS #
004514360
City
Birmingham
State
AL
Country
United States
Zip Code
35294
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