Date of Award

2003

Level of Access

Open-Access Thesis

Degree Name

Master of Science (MS)

Department

Zoology

Advisor

Harold B. Dowse

Second Committee Member

John M. Ringo

Third Committee Member

Erik Johnson

Abstract

There is a lack of information concerning the genetics of heart disease, especially of those due to aberrant pacemaker activity. Drosophila melanogaster is an ideal candidate for research in this area because of its suitability to genetic manipulation and its accessible genetic database. What is most compelling, however, is that the genesis of heartbeat is Drosophila is strikingly similar to that in many other organisms, including mammals. The myogenic heart of DrosophiIa melanogaster is stimulated to contract by a caudal pacemaker, which is regulated by ion channel interactions. A voltage-gated calcium channel of PIQ- or N-type is implicated in the pacemaker by pharmacological studies. The voltage-gated calcium channel a, subunit encoding gene in Drosophila, cacophony (cac), was identified as a candidate for this role. After examining heartbeat of the cac alleles cac^5 and cac^ts2 I report that they have increased heart rates and rhythmicities, potentially due to altered inactivation of the calcium channels they encode affecting pacemaking. The gene with which the RNA helicase mutant no action potential ^temperature-sensitive (mle^napts) interacts, causing arrhythmic heartbeat, has yet to be uncovered. mlenflP'5s an allele of the dosage compensation gene maleless (mle). It is possible that mle^napts is interacting with cac to cause deviations in heartbeat phenotype from wild-type. By characterizing heartbeat of cac ; mle^napts double mutants I determine that the genes interact, but in an unresolved manner.

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