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Originally published as Genetics Published Articles Ahead of Print on January 31, 2005.

Genetics, Vol. 169, 2137-2149, April 2005, Copyright © 2005
doi:10.1534/genetics.104.028357

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Drosophila couch potato Mutants Exhibit Complex Neurological Abnormalities Including Epilepsy Phenotypes

Edward Glasscock* and Mark A. Tanouye*,{dagger},1

* Department of Molecular and Cell Biology, Division of Neurobiology
{dagger} Department of Environmental Science, Policy and Management, Division of Insect Biology, University of California, Berkeley, California 94720

1 Corresponding author: Department of Environmental Science, Policy and Management, Life Sciences Addition, Room 131A, University of California, Berkeley, CA 94720.
E-mail: tanouye{at}uclink4.berkeley.edu

RNA-binding proteins play critical roles in regulation of gene expression, and impairment can have severe phenotypic consequences on nervous system function. We report here the discovery of several complex neurological phenotypes associated with mutations of couch potato (cpo), which encodes a Drosophila RNA-binding protein. We show that mutation of cpo leads to bang-sensitive paralysis, seizure susceptibility, and synaptic transmission defects. A new cpo allele called cpoEG1 was identified on the basis of a bang-sensitive paralytic mutant phenotype in a sensitized genetic background (sda/+). In heteroallelic combinations with other cpo alleles, cpoEG1 shows an incompletely penetrant bang-sensitive phenotype with ~30% of flies becoming paralyzed. In response to electroconvulsive shock, heteroallelic combinations with cpoEG1 exhibit seizure thresholds less than half that of wild-type flies. Finally, cpo flies display several neurocircuit abnormalities in the giant fiber (GF) system. The TTM muscles of cpo mutants exhibit long latency responses coupled with decreased following frequency. DLM muscles in cpo mutants show drastic reductions in following frequency despite exhibiting normal latency relationships. The labile sites appear to be the electrochemical GF-TTMn synapse and the chemical PSI-DLMn synapses. These complex neurological phenotypes of cpo mutants support an important role for cpo in regulating proper nervous system function, including seizure susceptibility.




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[Abstract] [Full Text] [PDF]


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