DOI: 10.1093/genetics/161.3.1197. Temperature-Sensitive Paralytic Mutants Are Enriched For Those Causing Neurodegeneration in Drosophila

Temperature-Sensitive Paralytic Mutants Are Enriched For Those Causing Neurodegeneration in Drosophila

10.1093/genetics/161.3.1197

Crossref journal-article

Oxford University Press (OUP)

Genetics (286)

Abstract

Abstract Age-dependent neurodegeneration is a pathological condition found in many metazoans. Despite the biological and medical significance of this condition, the cellular and molecular mechanisms underlying neurodegeneration are poorly understood. The availability of a large collection of mutants exhibiting neurodegeneration will provide a valuable resource to elucidate these mechanisms. We have developed an effective screen for isolating neurodegeneration mutants in Drosophila. This screen is based on the observation that neuronal dysfunction, which leads to observable behavioral phenotypes, is often associated with neurodegeneration. Thus, we used a secondary histological screen to examine a collection of mutants originally isolated on the basis of conditional paralytic phenotypes. Using this strategy, we have identified 15 mutations affecting at least nine loci that cause gross neurodegenerative pathology. Here, we present a genetic, behavioral, and anatomical analysis of vacuous (vacu), the first of these mutants to be characterized, and an overview of other mutants isolated in the screen. vacu is a recessive mutation located cytologically at 85D-E that causes locomotor defects in both larvae and adults as well as neuronal hyperactivity. In addition, vacu exhibits extensive age-dependent neurodegeneration throughout the central nervous system. We also identified mutations in at least eight other loci that showed significant levels of neurodegeneration with a diverse array of neuropathological phenotypes. These results demonstrate the effectiveness of our screen in identifying mutations causing neurodegeneration. Further studies of vacu and the other neurodegenerative mutants isolated should ultimately help dissect the biochemical pathways leading to neurodegeneration.

Bibliography

Palladino, M. J., Hadley, T. J., & Ganetzky, B. (2002). Temperature-Sensitive Paralytic Mutants Are Enriched For Those Causing Neurodegeneration in Drosophila. Genetics, 161(3), 1197â1208.

Authors 3

Michael J Palladino (first)
Tricia J Hadley (additional)
Barry Ganetzky (additional)

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Dates

Type	When
Created	4 years, 4 months ago (April 23, 2021, 12:58 a.m.)
Deposited	3 years, 7 months ago (Jan. 5, 2022, 11:12 a.m.)
Indexed	1 month, 1 week ago (July 20, 2025, 12:15 a.m.)
Issued	23 years, 2 months ago (July 1, 2002)
Published	23 years, 2 months ago (July 1, 2002)
Published Online	23 years, 2 months ago (July 1, 2002)
Published Print	23 years, 2 months ago (July 1, 2002)

Funders 0

None

BibTeX

@article{Palladino_2002, title={Temperature-Sensitive Paralytic Mutants Are Enriched For Those Causing Neurodegeneration in Drosophila}, volume={161}, ISSN={1943-2631}, url={http://dx.doi.org/10.1093/genetics/161.3.1197}, DOI={10.1093/genetics/161.3.1197}, number={3}, journal={Genetics}, publisher={Oxford University Press (OUP)}, author={Palladino, Michael J and Hadley, Tricia J and Ganetzky, Barry}, year={2002}, month=jul, pages={1197–1208} }

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