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Review
. 2022 Dec 28;14(1):87.
doi: 10.3390/genes14010087.

Drosophila melanogaster as a Model to Study Fragile X-Associated Disorders

Jelena Trajković  1 , Vedrana Makevic  2 , Milica Pesic  3 , Sofija Pavković-Lučić  1 , Sara Milojevic  4 , Smiljana Cvjetkovic  5 , Randi Hagerman  6   7 , Dejan B Budimirovic  8   9 , Dragana Protic  4
Affiliations
Review

Drosophila melanogaster as a Model to Study Fragile X-Associated Disorders

Jelena Trajković et al. Genes (Basel). .

Abstract

Fragile X syndrome (FXS) is a global neurodevelopmental disorder caused by the expansion of CGG trinucleotide repeats (≥200) in the Fragile X Messenger Ribonucleoprotein 1 (FMR1) gene. FXS is the hallmark of Fragile X-associated disorders (FXD) and the most common monogenic cause of inherited intellectual disability and autism spectrum disorder. There are several animal models used to study FXS. In the FXS model of Drosophila, the only ortholog of FMR1, dfmr1, is mutated so that its protein is missing. This model has several relevant phenotypes, including defects in the circadian output pathway, sleep problems, memory deficits in the conditioned courtship and olfactory conditioning paradigms, deficits in social interaction, and deficits in neuronal development. In addition to FXS, a model of another FXD, Fragile X-associated tremor/ataxia syndrome (FXTAS), has also been established in Drosophila. This review summarizes many years of research on FXD in Drosophila models.

Keywords: Drosophila melanogaster; FMR1 gene; FMRP; FXTAS; Fragile X syndrome.

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Conflict of interest statement

Dejan B. Budimirovic has received funding from Zynerba Pharmaceuticals (ZYN2-CL-017, ZYN2-CL-033) as a principal investigator on clinical trials in FXS. He also consulted on clinical trial outcome measures in FXS (Seaside, Ovid). All the above funding has been directed to the Kennedy Krieger Institute/the Johns Hopkins Medical Institutions; Dejan B. Budimirovic receives no personal funds, and the Institute has no relevant financial interest in any of the commercial entities listed. Other authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Functions and localization of dFMRP in D. melanogaster (adapted from reference [21]) Aberrations: dfmr1-Fragile X Messenger Ribonucleoprotein 1 gene in Drosophila; dFMRP-dfmr1 protein in D. melanogaster.
Figure 2
Figure 2
Drosophila model of fragile X syndrome (adapted from reference [21]). Aberrations: dfmr1-Fragile X Messenger Ribonucleoprotein 1 gene in Drosophila; dFMRP-dfmr1 protein in Drosophila).
Figure 3
Figure 3
Major phenotypes in humans with FXS and overlapping loss-of-function phenotypes in dfmr1 mutants.
Figure 4
Figure 4
An example of the study of circadian rhythms in Drosophila using the software. (The image is from Protic’s lab: www.polyfrax.com, accessed on 1. December 2022.). A multi-well plate was prepared. Depending on experimental needs, the plates can be 24-, 48-, or 96- well. The flies were placed individually in each well, and an air-permeable cover was put over the top of the well plate. The flies were then individually housed in a humid environment with some available nutrition. The well plate was loaded with flies and inserted into the system’s chamber. The software was set up to control the environment (temperature and lighting) and the measure of the distance traveled by each fly. The white cycles show the flies as software targets in 24 wells. The activity (measured as distance traveled) is measured and recorded as data during the experiment.
See this image and copyright information in PMC

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