Investigating Developmental and Epileptic Encephalopathy Using Drosophila melanogaster

Abstract

Developmental and epileptic encephalopathies (DEEs) are the spectrum of severe epilepsies characterized by early-onset, refractory seizures occurring in the context of developmental regression or plateauing. Early infantile epileptic encephalopathy (EIEE) is one of the earliest forms of DEE, manifesting as frequent epileptic spasms and characteristic electroencephalogram findings in early infancy. In recent years, next-generation sequencing approaches have identified a number of monogenic determinants underlying DEE. In the case of EIEE, 85 genes have been registered in Online Mendelian Inheritance in Man as causative genes. Model organisms are indispensable tools for understanding the in vivo roles of the newly identified causative genes. In this review, we first present an overview of epilepsy and its genetic etiology, especially focusing on EIEE and then briefly summarize epilepsy research using animal and patient-derived induced pluripotent stem cell (iPSC) models. The Drosophila model, which is characterized by easy gene manipulation, a short generation time, low cost and fewer ethical restrictions when designing experiments, is optimal for understanding the genetics of DEE. We therefore highlight studies with Drosophila models for EIEE and discuss the future development of their practical use.

Investigating rare and ultrarare epilepsy syndromes with Drosophila models

“…Forward genetic screens in Drosophila have identified factors affecting general functions such as sleep 23 as well as many that associate with ID and autism spectrum disorder 24 . With respect to epilepsy, geneticists and clinicians have identified causative variants in more than 100 genes, the majority of which have conserved orthologs in Drosophila , enabling fast and inexpensive modeling of human patients’ conditions 25 , 26 . Even the intricate role of glial cell contribution to hereditary epilepsies has been investigated through interactions that have been conserved on the level of both molecular and cellular interactions 27 , 28 .…”

Avaliação do efeito carcinogênico do bromazepam em Drosophila melanogaster

“…A deleção desse gene proporciona o desenvolvimento de clones de células arredondadas e consideravelmente invasivas, caracterizadas como verrugas (warts) que se propagam por todo o corpo da mosca (EEKEN et al, 2002;JUSTICE et al, 1995). Além da relativa conservação evolutiva entre mamíferos e a Drosophila, as moscas das frutas são de fácil manuseio, possuem período de vida curto, alta reprodutividade e baixo custo de cultivo, fatores que tornam vantajosa sua utilização como modelo experimental (GRIFFITHS et al, 2016;NEPOMUCENO, 2015;TAKAI et al, 2020). A mosca é utilizada desde 1906 em estudos de genética, visto que seus genes possuem cerca de 60% de homologia com os genes de doenças humanas (TONI et al, 2002).…”

The international exchange of Drosophila melanogaster strains

“…Transgenic technologies have enabled geneticists to substitute human genes for fly genes in the flies themselves, and these 'humanised' flies are proving particularly important for dissecting the functions of protein domains and examining the effects of protein−drug interactions. Age-related disorders [8] Alcoholism [9] Alzheimer's disease [10,11] Amyotrophic lateral sclerosis [12,13] Angelman syndrome [14] Autism spectrum disorder [15] Cancer [16] Cardiomyopathies and other heart diseases [17,18] Cystic fibrosis [19] Diabetes [20] Epilepsy and other seizure disorders [21,22] Fragile X syndrome [23] Galactosaemia [24] Huntington's disease [25] Inflammatory bowel disease [26] Intellectual disability [27] Kidney diseases [28] Lysosomal storage diseases [29] Metabolic disorders and syndromes [30] Microcephaly [31] Mitochondrial-related disorders [32] Muscular dystrophies [33] Myotonic dystrophy [34] Neurofibromatosis [35] Obesity [30] Parkinson's disease [36] Creutzfeld-Jakob disease [37] Retinitis pigmentosa [38] Sleep disorders [39] Spinal muscular atrophy [40] Spinocerebellar ataxia [41,42] The unrestricted exchange of stocks has been formalised through the establishment of public repositories that distribute useful stocks. The center managed by the authors − the Bloomington Drosophila Stock Center (BDSC) at Indiana University − is the largest.…”