Mediators of a long-term movement abnormality in a Drosophila melanogaster model of classic galactosemia
| Autor: | Brian DuBoff, Judith L. Fridovich-Keil, Mel B. Feany, Emily L. Ryan |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2012 |
| Předmět: |
Galactosemias
Startle response Aging Reflex Startle Time Factors Movement Neuroscience (miscellaneous) lcsh:Medicine Medicine (miscellaneous) Motor Activity Bioinformatics General Biochemistry Genetics and Molecular Biology 03 medical and health sciences 0302 clinical medicine Immunology and Microbiology (miscellaneous) lcsh:Pathology medicine Animals Drosophila Proteins Humans 030304 developmental biology Genetics 0303 health sciences Dyskinesias biology medicine.diagnostic_test Muscles lcsh:R Galactosemia Galactosephosphates Brain Galactose biology.organism_classification medicine.disease Galactosyltransferases Phenotype Pathophysiology 3. Good health Diet Disease Models Animal Drosophila melanogaster Abnormality Complication 030217 neurology & neurosurgery Drosophila Protein lcsh:RB1-214 Research Article |
| Zdroj: | Disease Models & Mechanisms Disease Models & Mechanisms, Vol 5, Iss 6, Pp 796-803 (2012) |
| ISSN: | 1754-8411 1754-8403 |
| Popis: | Summary Despite neonatal diagnosis and life-long dietary restriction of galactose, many patients with classic galactosemia grow to experience significant long-term complications. Among the more common are speech, cognitive, behavioral, ovarian, and neurological/movement difficulties. Despite decades of research, the pathophysiology of these long-term complications remains obscure, hindering prognosis and attempts at improved intervention. As a first step to overcome this roadblock we have begun to explore long-term outcomes in our previously reported GALT-null Drosophila melanogaster model of classic galactosemia. Here we describe the first of these studies. Using a countercurrent device, a simple climbing assay, and a startle response test to characterize and quantify an apparent movement abnormality, we explored the impact of cryptic GALT expression on phenotype, tested the role of sub-lethal galactose exposure and galactose-1-phosphate (gal-1P) accumulation, tested the impact of age, and searched for potential anatomical defects in brain and muscle. We found that about 2.5% residual GALT activity was sufficient to reduce outcome severity. Surprisingly, sub-lethal galactose exposure and gal-1P accumulation during development showed no effect on adult phenotype. Finally, despite the apparent neurological or neuromuscular nature of the complication we found no clear morphological differences between mutants and controls in brain or muscle, suggesting that the defect is subtle and/or may be physiologic rather than structural. Combined, our results confirm that, like human patients, GALT-null Drosophila experience significant long-term complications that occur independent of galactose exposure, and serve as a proof of principle demonstrating utility of the GALT-null Drosophila model as a tool to explore genetic and environmental modifiers of long-term outcome in GALT deficiency. |
| Databáze: | OpenAIRE |
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