Understanding fragile X syndrome: insights from animal models.
The fragile X mental retardation syndrome is caused by large methylated expansions of a CGG repeat in the FMR1 gene leading to the loss of expression of FMRP, an RNA-binding protein. FMRP is proposed to act as a regulator of mRNA transport or translation that plays a role in synaptic maturation and function. To study the physiological function of the FMR1 protein, mouse and Drosophila models have been developed. The loss-of-function mouse model shows slightly enlarged testes, a subtle behavioral phenotype, and discrete anomalies of dendrite spines similar to those observed in brains of patients. Studies in Drosophila indicate that FXMR plays an important role in synaptogenesis and axonal arborization, which may underlie the observed deficits in flight ability and circadian behavior of FXR mutant flies. The relevance of these studies to our understanding of fragile X syndrome is discussed.
Bakker
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CE
Department of Clinical Genetics, Erasmus MC, Rotterdam, The Netherlands.
Oostra
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BA
D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D004195:Disease Models, Animal; D004330:Drosophila / Q000235:genetics / Q000502:physiology; D051860:Fragile X Messenger Ribonucleoprotein 1; D005600:Fragile X Syndrome / Q000235:genetics* / Q000503:physiopathology; D006801:Humans; D051379:Mice; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics*; D016601:RNA-Binding Proteins; D019680:Trinucleotide Repeat Expansion / Q000235:genetics*
D051860:Fragile X Messenger Ribonucleoprotein 1; D009419:Nerve Tissue Proteins; D016601:RNA-Binding Proteins; C497683:FMR1 protein, human; C497684:Fmr1 protein, mouse