Effects of tyrosine hydroxylase mutants on locomotor activity in Drosophila: A study in functional genomics

Pendleton, R. G., Rasheed, A., Sardina, T., Tully, T., Hillman, R. (March 2002) Effects of tyrosine hydroxylase mutants on locomotor activity in Drosophila: A study in functional genomics. Behavior Genetics, 32 (2). pp. 89-94. ISSN 0001-8244

URL: http://www.ncbi.nlm.nih.gov/pubmed/12036114
DOI: 10.1023/A:1015279221600

Abstract

The brain of the adult fruit fly, Drosophila melanogaster, contains tyrosine hydroxylase, the rate-limiting enzyme required for catecholamine biosynthesis, as well as dopa decarboxylase. Catecholamines, principally dopamine, are also present. We have previously shown that pharmacological inhibition of tyrosine hydroxylase with α-methyl-p-tyrosine results in a dose-related inhibition of locomotor activity in adult organisms. Similar results were found with reserpine, a well-known inhibitor of catecholamine uptake into storage granules. The drug-induced inhibition could be prevented in each case by the concomitant administration of l-dopa. The single-copy gene coding for tyrosine hydroxylase in Drosophila is pale (ple). Both null and temperature-sensitive loss of function mutant alleles of ple are recessive embryonic lethals. Heterozygous null mutant flies have normal locomotor activity demonstrating that only a single dose of the wild type form of ple is required to support normal function. Both hemizygous and homozygous temperature-sensitive ple mutants (ple ts1 ) also show normal locomotor activity at the permissive temperature for this mutant allele (18°C), which progressively declines as the temperature is increased to its restrictive level (29°C). These abnormal locomotor effects are reversible by l-dopa. Thus the effects on locomotor activity resulting from the pharmacological inhibition of catecholamine synthesis or storage are the same as those resulting from lack of tyrosine hydroxylase expression. These findings indicate that brain catecholamine loss decreases locomotor activity in the fly, as it does in mammals, and demonstrate the ability of functional genomic studies to mimic that of pharmacological inhibition of enzyme function or other similar processes.

Item Type: Paper
Subjects: bioinformatics
organism description > animal > insect > Drosophila
bioinformatics > genomics and proteomics
CSHL Authors:
Communities: CSHL labs > Tully lab
Depositing User: Matt Covey
Date: March 2002
Date Deposited: 31 Oct 2013 20:18
Last Modified: 31 Oct 2013 20:18
Related URLs:
URI: http://repository.cshl.edu/id/eprint/28767

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