Efficient strategies based on behavioral and electrophysiological methods for epilepsy-related gene screening in the Drosophila model

Liu, Chu-Qiao; Qu, Xiao-Chong; He, Ming-Feng; Liang, Dehai; Xie, Shiming; Zhang, Xi-Xing; Lin, Yong-Miao; Zhang, Wenjun; Wu, Kaijin; Qiao, Jing‐Da

doi:10.3389/fnmol.2023.1121877

Cited by 2 publications

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References 61 publications

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“…To evaluate the role of Z fh2 deficiency in development, the body length of fly larvae was assessed, as in our previous study. 27 The larval stages of flies can be divided into three stages, i.e., the first (24 h), second (48 h), and third (72 h) instar larvae. The length of the larvae was measured using ImageJ NIH software (https://imagej.nih.gov/ij/).…”

Section: Methodsmentioning

confidence: 99%

“…To evaluate the role of Z fh2 deficiency in development, the body length of the fly larvae was assessed as described in our previous study. [28] A bang sensitivity assay was conducted on flies 3-5 days after eclosion to evaluate the seizure-like behavior. [8] The duration and percentage of seizure-like behavior were recorded as described in our previous study.…”

Section: Methodsmentioning

confidence: 99%

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ZFHX3variants cause childhood partial epilepsy and infantile spasms with favorable outcomes

Luo

Wang

et al. 2023

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Background: TheZFHX3gene is highly expressed in the developing brain and plays vital roles in embryonic development, cell proliferation, neuronal differentiation, and neuronal death. The association between theZFHX3gene and human disease was undefined. This study aims to explore the relationship betweenZFHX3variants and epilepsy. Methods: Whole-exome sequencing was performed in patients with partial epilepsy without acquired causes.Drosophilamodel ofZfh2(ortholog ofZFHX3) knockdown was used to validate the association betweenZFHX3and epilepsy. The expression level ofZFHX3in different developmental stages was analyzed by using the data in humans from the Brainspan database and in flies and mice determined by RT-qPCR. Results: Eight pairs of compound heterozygous variants inZFHX3were identified in eight unrelated cases of childhood epilepsies. All patients presented partial epilepsy, including two with early spasms and one with frequent nonconvulsive status epilepticus. The three cases with severe epilepsies also had neurodevelopmental abnormities. However, all patients became seizure-free, including the patients with spasms. These variants had no or low allele frequencies in controls and presented statistically higher frequency in the case cohort than the controls. The number of recessiveZFHX3variants identified in this cohort was significantly more than the expected number of the East Asian population and that of the control of 1942 asymptomatic parents. Variants were predicted to be damaging by protein modeling and/or in silico prediction tools. Genotype-phenotype correlation analysis revealed that the patients with missense variants in C-terminus or C-terminus-truncated variant exhibited mild phenotype (only partial epilepsy). Knockdown ofZfh2in flies led to increased susceptibility to seizures and abnormal firing of excitability neurons. InDrosophila, the expression ofZfh2is high in larvae, decreased in pupae and early adults, and increased in later adults. In mice,Zfhx3is predominantly expressed in fetuses and decreased dramatically after birth. In humans, the data from the Brainspan database showed thatZFHX3is highly expressed in the embryonic period and decreased after birth with a nadir at approximately 10 years old. The dramatical decreasing ofZFHX3in early life correlated with the natural course of the illness. Conclusion:ZFHX3variants were potentially associated with partial epilepsy of childhood and infant spasms. The correlation between the outcome and gene expression stage provided insight into the underlying mechanism of the natural course of illness, potentially being helpful in management of the patients.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

ZFHX3variants cause childhood partial epilepsy and infantile spasms with favorable outcomes

Luo

Wang

et al. 2023

Preprint

Self Cite

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UBR4 deficiency causes male sterility and testis abnormal in Drosophila

et al. 2023

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IntroductionIt has been established that UBR4 encodes E3 ubiquitin ligase, which determines the specificity of substrate binding during protein ubiquitination and has been associated with various functions of the nervous system but not the reproductive system. Herein, we explored the role of UBR4 on fertility with a Drosophila model.MethodsDifferent Ubr4 knockdown flies were established using the UAS/GAL4 activating sequence system. Fertility, hatchability, and testis morphology were studied, and bioinformatics analyses were conducted. Our results indicated that UBR4 deficiency could induce male sterility and influent egg hatchability in Drosophila.ResultsWe found that Ubr4 deficiency affected the testis during morphological analysis. Proteomics analysis indicated 188 upregulated proteins and 175 downregulated proteins in the testis of Ubr4 knockdown flies. Gene Ontology analysis revealed significant upregulation of CG11598 and Sfp65A, and downregulation of Pelota in Ubr4 knockdown flies. These proteins were involved in the biometabolic or reproductive process in Drosophila. These regulated proteins are important in testis generation and sperm storage promotion. Bioinformatics analysis verified that UBR4 was low expressed in cryptorchidism patients, which further supported the important role of UBR4 in male fertility.DiscussionOverall, our findings suggest that UBR4 deficiency could promote male infertility and may be involved in the protein modification of UBR4 by upregulating Sfp65A and CG11598, whereas downregulating Pelota protein expression.

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Efficient strategies based on behavioral and electrophysiological methods for epilepsy-related gene screening in the Drosophila model

Cited by 2 publications

References 61 publications

ZFHX3variants cause childhood partial epilepsy and infantile spasms with favorable outcomes

ZFHX3variants cause childhood partial epilepsy and infantile spasms with favorable outcomes

UBR4 deficiency causes male sterility and testis abnormal in Drosophila

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