Abstracts
Fragile X Syndrome: Use of zebrafish to Explore Developmental Origins and Potential Treatments
Ben Tucker
PhD Student, University of Adelaide, Discipline of Genetics
Supervised through Genetics, University of Adelaide
Fragile X Syndrome (FRAXA) is a form of mental retardation caused by a gene defect. The defect causes loss of the FMR1 protein that is needed in the brain for normal development. Fragile X Syndrome is one of the most frequent inherited forms of mental retardation (~1 in 4000 males; ~1 in 8000 females). It is also associated with other problems including craniofacial abnormalities, enhanced sensitivity to sensory stimuli and some epileptic and autistic behaviours. Existing genetic models of the disease (mouse and banana fly) indicate that the behavioural abnormalities associated with the condition may be due to abnormal connections between neurons, related to abnormal neuron shape. The zebrafish embryo is an important addition to these models since it is transparent and develops outside the mother (enabling direct observation of development in living tissues) and provides a highly efficient means for drug screening (drugs can be applied directly to the fish water). We have discovered that we can recapitulate the neurite defects found in the other model organisms in a zebrafish model of FRAXA. Uniquely, these embryos also present craniofacial defects that appear to model elements of the syndrome5.
In the mouse model, behavioural abnormalities have been ameliorated by application of a drug (2-methyl-6-(phenylethynyl)-pyridine; MPEP). We found that application of this drug to our zebrafish model completely rescues the abnormal neurite shape. This shows that the zebrafish embryo model can be used to screen a wider range of therapeutic agents to find potential treatments for Fragile X Syndrome symptoms in humans.
