The aim of this project is to characterize and isolate genes that are relevant in maintaining the proper function and integrity of the human nervous system, specifically genes associated with neurodegenerative diseases, by using the power of Drosophila genetics. Based on the fact that brain degeneration tends to be associated with reduced lifetime, systematic screens for short-life Drosophila mutants were carried out by P-element insertions and ethyl methane sulfonate (EMS) mutagenesis. The brain pathologies of short-life mutants were examined by microscopy, and then compared with certain human brain degenerative diseases. We found five brain degenerative mutants. bubblegum, spongecake, eggroll, chocolate chip, and meringue were named by virtue of their brain lesions. The bubblegum mutant fly has high levels of accumultaion of very long chain fatty acids, which is similar to human adrenoleukodystrophy. spongecake shows vacuoles in the optic lobe neuropil region, eggroll exhibits abnormal multilamellated inclusions in its brain and chocolate chip undergoes degeneration in the cortex. Retinal degeneration occurs as the meringue mutant ages.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Intramural Research (Z01)
Project #
1Z01NS002988-01
Application #
6413877
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
1
Fiscal Year
2000
Total Cost
Indirect Cost
City
State
Country
United States
Zip Code
Chang, Karen T; Min, Kyung-Tai (2005) Drosophila melanogaster homolog of Down syndrome critical region 1 is critical for mitochondrial function. Nat Neurosci 8:1577-85
Taylor, J Paul; Taye, Addis A; Campbell, Catherine et al. (2003) Aberrant histone acetylation, altered transcription, and retinal degeneration in a Drosophila model of polyglutamine disease are rescued by CREB-binding protein. Genes Dev 17:1463-8
Chang, Karen T; Shi, Yi-Jun; Min, Kyung-Tai (2003) The Drosophila homolog of Down's syndrome critical region 1 gene regulates learning: implications for mental retardation. Proc Natl Acad Sci U S A 100:15794-9
Kang, Hyung-Lyun; Benzer, Seymour; Min, Kyung-Tai (2002) Life extension in Drosophila by feeding a drug. Proc Natl Acad Sci U S A 99:838-43
Chang, Karen T; Min, Kyung-Tai (2002) Regulation of lifespan by histone deacetylase. Ageing Res Rev 1:313-26