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学者姓名：陈文锋
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Abstract ：
Certain amino acids changes in the human Na+/K+-ATPase pump, ATPase Na+/K+ transporting subunit alpha 1 (ATP1A1), cause Charcot-Marie-Tooth disease type 2 (CMT2) disease and refractory seizures. To develop in vivo models to study the role of Na+/K+-ATPase in these diseases, we modified the Drosophila gene homolog, Atp alpha, to mimic the human ATP1A1 gene mutations that cause CMT2. Mutations located within the helical linker region of human ATP1A1 (I592T, A597T, P600T, and D601F) were simultaneously introduced into endogenous DrosophilaAtp alpha by CRISPR/Cas9-mediated genome editing, generating the Atp alpha(TTTF) model. In addition, the same strategy was used to generate the corresponding single point mutations in flies (Atp alpha(I571T), Atp alpha(A576T), Atp alpha(P579T), and Atp alpha(D580F)). Moreover, a deletion mutation (Atp alpha(mut)) that causes premature termination of translation was generated as a positive control. Of these alleles, we found two that could be maintained as homozygotes (Atp alpha(I571T) and Atp alpha(P579T)). Three alleles (Atp alpha(A576T), Atp alpha(P579) and Atp alpha(D580F)) can form heterozygotes with the Atp alpha(mut) allele. We found that the Atp alpha allele carrying these CMT2-associated mutations showed differential phenotypes in Drosophila. Flies heterozygous for Atp alpha(TTTF) mutations have motor performance defects, a reduced lifespan, seizures, and an abnormal neuronal morphology. These Drosophila models will provide a new platform for studying the function and regulation of the sodium-potassium pump.
Keyword ：
Atp alpha Atp alpha bang-sensitive paralysis bang-sensitive paralysis Charcot-Marie-Tooth disease type 2 Charcot-Marie-Tooth disease type 2 CRISPR/Cas9 CRISPR/Cas9 homology-directed repair homology-directed repair Na+/K+-ATPase Na+/K+-ATPase point mutation point mutation seizures seizures sodium pump sodium pump
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| GB/T 7714 | Yuan, Yao , Yu, Lingqi , Zhuang, Xudong et al. Drosophila models used to simulate human ATP1A1 gene mutations that cause Charcot-Marie-Tooth type 2 disease and refractory seizures [J]. | NEURAL REGENERATION RESEARCH , 2025 , 20 (1) : 265-276 . |
| MLA | Yuan, Yao et al. "Drosophila models used to simulate human ATP1A1 gene mutations that cause Charcot-Marie-Tooth type 2 disease and refractory seizures" . | NEURAL REGENERATION RESEARCH 20 . 1 (2025) : 265-276 . |
| APA | Yuan, Yao , Yu, Lingqi , Zhuang, Xudong , Wen, Dongjing , He, Jin , Hong, Jingmei et al. Drosophila models used to simulate human ATP1A1 gene mutations that cause Charcot-Marie-Tooth type 2 disease and refractory seizures . | NEURAL REGENERATION RESEARCH , 2025 , 20 (1) , 265-276 . |
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Congenital stationary night blindness (CSNB) is a genetically heterogeneous inherited retinal disorder, caused by over 300 mutations in 17 different genes. While there are numerous fly models available for simulating ocular diseases, most are focused on mimicking retinitis pigmentosa (RP), with animal models specifically addressing CSNB limited to mammals. Here, we present a CSNB fly model associated with the mtt gene, utilizing RNA interference (RNAi) to silence the mtt gene in fly eyes (homologous to the mammalian GRM6 gene) and construct a CSNB model. Through this approach, we observed significant defects in the eye structure and function upon reducing mtt expression in fly eyes. This manifested as disruptions in the compound eye lens structure and reduced sensitivity to light responses. These results suggest a critical role for mtt in the function of fly adult eyes. Interestingly, we found that the mtt gene is not expressed in the photoreceptor neurons of adult flies but is localized to the inner lamina neurons. In summary, these results underscore the crucial involvement of mtt in fly retinal function, providing a framework for understanding the pathogenic mechanisms of CSNB and facilitating research into potential therapeutic interventions.
Keyword ：
CSNB CSNB Drosophila Drosophila eye eye GRM6 GRM6 mtt mtt retina retina
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| GB/T 7714 | Chen, Wenfeng , Zhong, Wenmiao , Yu, Lingqi et al. A Drosophila Model Reveals the Potential Role for mtt in Retinal Disease [J]. | INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES , 2024 , 25 (2) . |
| MLA | Chen, Wenfeng et al. "A Drosophila Model Reveals the Potential Role for mtt in Retinal Disease" . | INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES 25 . 2 (2024) . |
| APA | Chen, Wenfeng , Zhong, Wenmiao , Yu, Lingqi , Lin, Xiang , Xie, Jiayu , Liu, Zhenxing . A Drosophila Model Reveals the Potential Role for mtt in Retinal Disease . | INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES , 2024 , 25 (2) . |
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Earth's rotation shapes a 24-h cycle, governing circadian rhythms in organisms. In mammals, the core clock genes, CLOCK and BMAL1, are regulated by PERIODs (PERs) and CRYPTOCHROMEs (CRYs), but their roles remain unclear in the diamondback moth, Plutella xylostella. To explore this, we studied P. xylostella, which possesses a simplified circadian system compared to mammals. In P. xylostella, we observed rhythmic expressions of the Pxper and Pxcry2 genes in their heads, with differing phases. In vitro experiments revealed that PxCRY2 repressed monarch butterfly CLK:BMAL1 transcriptional activation, while PxPER and other CRY-like proteins did not. However, PxPER showed an inhibitory effect on PxCLK/PxCYCLE. Using CRISPR/Cas9, we individually and in combination knocked out Pxper and Pxcry2, then conducted gene function studies and circadian transcriptome sequencing. Loss of either Pxper or Pxcry2 eliminated the activity peak after lights-off in light-dark cycles, and Pxcry2 loss reduced overall activity. Pxcry2 was crucial for maintaining endogenous rhythms in constant darkness. Under light-dark conditions, 1 098 genes exhibited rhythmic expression in wild-type P. xylostella heads, with 749 relying on Pxper and Pxcry2 for their rhythms. Most core clock genes lost their rhythmicity in Pxper and Pxcry2 mutants, while Pxcry2 sustained rhythmic expression, albeit with reduced amplitude and altered phase. Additionally, rhythmic genes were linked to biological processes like the spliceosome and Toll signaling pathway, with these rhythms depending on Pxper or Pxcry2 function. In summary, our study unveils differences in circadian rhythm regulation by Pxper and Pxcry2 in P. xylostella. This provides a valuable model for understanding circadian clock regulation in nocturnal animals. The earth's rotation drives a roughly 24-h cycle, governing circadian rhythms in organisms. In mammals, master genes CLOCK:BMAL1 are repressed by multiple PERIODs (PERs) and CRYPTOCHROMEs (CRYs). Differences in the regulation of behavior by and oscillations in PERs and CRYs are not known. Plutella xylostella, the diamondhead moth, possessing a simplified PER/CRY system, was investigated. Here, we applied the CRISPR/Cas9 technology to individually and in combination knock out the circadian clock genes of Pxper and Pxcry2. Subsequently, we conducted in vivo gene function studies, coupled with time-series transcriptome sequencing to analyze the functional differences of Pxper and Pxcry2. # image
Keyword ：
CRY2 CRY2 daily transcriptome daily transcriptome locomotor behavior locomotor behavior PERIOD PERIOD Plutella xylostella Plutella xylostella
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| GB/T 7714 | Chen, Wenfeng , Wang, Danfeng , Yu, Lingqi et al. Comparative analysis of locomotor behavior and head diurnal transcriptome regulation by PERIOD and CRY2 in the diamondback moth [J]. | INSECT SCIENCE , 2024 . |
| MLA | Chen, Wenfeng et al. "Comparative analysis of locomotor behavior and head diurnal transcriptome regulation by PERIOD and CRY2 in the diamondback moth" . | INSECT SCIENCE (2024) . |
| APA | Chen, Wenfeng , Wang, Danfeng , Yu, Lingqi , Zhong, Wenmiao , Yuan, Yao , Yang, Guang . Comparative analysis of locomotor behavior and head diurnal transcriptome regulation by PERIOD and CRY2 in the diamondback moth . | INSECT SCIENCE , 2024 . |
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Aggregation of aberrant proteins is a common pathological hallmark in neurodegeneration such as polyglutamine (polyQ) and other repeat-expansion diseases. Here through overexpression of ataxin3 C-terminal polyQ expansion in Drosophila gut enterocytes, we generated an intestinal obstruction model of spinocerebellar ataxia type3 (SCA3) and reported a new role of nuclear-associated endosomes (NAEs)-the delivery of polyQ to the nucleoplasm. In this model, accompanied by the prominently increased RAB5-positive NAEs are abundant nucleoplasmic reticulum enriched with polyQ, abnormal nuclear envelope invagination, significantly reduced endoplasmic reticulum, indicating dysfunctional nucleocytoplasmic trafficking and impaired endomembrane organization. Consistently, Rab5 but not Rab7 RNAi further decreased polyQ-related NAEs, inhibited endomembrane disorganization, and alleviated disease model. Interestingly, autophagic proteins were enriched in polyQ-related NAEs and played non-canonical autophagic roles as genetic manipulation of autophagic molecules exhibited differential impacts on NAEs and SCA3 toxicity. Namely, the down-regulation of Atg1 or Atg12 mitigated while Atg5 RNAi aggravated the disease phenotypes both in Drosophila intestines and compound eyes. Our findings, therefore, provide new mechanistic insights and underscore the fundamental roles of endosome-centered nucleocytoplasmic trafficking and homeostatic endomembrane allocation in the pathogenesis of polyQ diseases.
Keyword ：
Autophagy Autophagy Endosome Endosome Inclusion body Inclusion body Non-canonical role of ATG Non-canonical role of ATG Nucleocytoplasmic trafficking Nucleocytoplasmic trafficking Spinocerebellar ataxia Spinocerebellar ataxia
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| GB/T 7714 | Nan, Yuyu , Chen, Wenfeng , Chen, Fei et al. Endosome mediated nucleocytoplasmic trafficking and endomembrane allocation is crucial to polyglutamine toxicity [J]. | CELL BIOLOGY AND TOXICOLOGY , 2024 , 40 (1) . |
| MLA | Nan, Yuyu et al. "Endosome mediated nucleocytoplasmic trafficking and endomembrane allocation is crucial to polyglutamine toxicity" . | CELL BIOLOGY AND TOXICOLOGY 40 . 1 (2024) . |
| APA | Nan, Yuyu , Chen, Wenfeng , Chen, Fei , Wei, Lili , Zeng, Aiyuan , Lin, Xiaohui et al. Endosome mediated nucleocytoplasmic trafficking and endomembrane allocation is crucial to polyglutamine toxicity . | CELL BIOLOGY AND TOXICOLOGY , 2024 , 40 (1) . |
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Abnormal accumulation of alpha synuclein (alpha-Syn) in sporadic and familial Parkinson's disease (PD) may be a key step in its pathogenesis. In this study, the expression matrix of the GSE95427 dataset after alpha-Syn overexpression in human glioma cell line H4 was obtained from the GEO database. We used the Gene Set Enrichment Analysis (GSEA) method to reanalyze this dataset to evaluate the possible functions of alpha-Syn. The results showed that the tumor necrosis factor alpha (TNF-alpha) signal was significantly activated in alpha-Syn-overexpressing cells, and oxidative phosphorylation signal, extracellular matrix signal, cell cycle related signal and fatty acid metabolism signal were significantly inhibited. Moreover, we employed the alpha-Syn-expressing transgenic Drosophila model of Parkinson's disease and knocked-down eiger, a TNF superfamily ligand homologue, indicating that the TNF-alpha pathway plays a role in the common pathogenesis of synucleinopathies. Our analysis based on GSEA data provides more clues for a better understanding of alpha-Syn function.
Keyword ：
alpha-Synuclein alpha-Synuclein Drosophila Drosophila gene set enrichment analysis gene set enrichment analysis Parkinson's disease Parkinson's disease signal pathway signal pathway
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| GB/T 7714 | Huang, Yusong , Wen, Dongjing , Yuan, Yao et al. Gene Set Enrichment Analysis and Genetic Experiment Reveal Changes in Cell Signaling Pathways Induced by alpha-Synuclein Overexpression [J]. | BIOMEDICINES , 2023 , 11 (2) . |
| MLA | Huang, Yusong et al. "Gene Set Enrichment Analysis and Genetic Experiment Reveal Changes in Cell Signaling Pathways Induced by alpha-Synuclein Overexpression" . | BIOMEDICINES 11 . 2 (2023) . |
| APA | Huang, Yusong , Wen, Dongjing , Yuan, Yao , Chen, Wenfeng . Gene Set Enrichment Analysis and Genetic Experiment Reveal Changes in Cell Signaling Pathways Induced by alpha-Synuclein Overexpression . | BIOMEDICINES , 2023 , 11 (2) . |
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腓骨肌萎缩症(Charcot-Marie-Tooth, CMT)通常是由神经元中某些蛋白质缺陷引起的一种常见家族遗传性外周神经系统疾病,患者表现为远端感觉和运动神经元的缺陷,行动能力不足,严重者可丧失行动能力。根据临床和电生理特征, CMT主要分为原发性脱髓鞘病变CMT1、原发性轴突病变CMT2以及继发性脱髓鞘和轴突病变的DI-CMT。越来越多的研究利用果蝇模型来模拟人类疾病和人类健康相关过程的各个方面。果蝇没有被髓鞘包围的轴突,因此不适合建立脱髓鞘型的CMT模型,而比较适合轴突病变CMT2的研究。该文主要针对CMT2进行分析,总结了人类CMT2涉及的相关致病基因,以及如何利用果蝇模型进行CMT2模型构建和病理分析。这对于CMT2疾病的生物学和医学研究具有重要的意义。
Keyword ：
CMT2 CMT2 果蝇 果蝇 疾病模型 疾病模型 腓骨肌萎缩症 腓骨肌萎缩症
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| GB/T 7714 | 余凌奇 , 谢甲钰 , 原垚 et al. 利用果蝇模型研究人类Ⅱ型腓骨肌萎缩症的进展 [J]. | 中国细胞生物学学报 , 2023 , 45 (01) : 122-132 . |
| MLA | 余凌奇 et al. "利用果蝇模型研究人类Ⅱ型腓骨肌萎缩症的进展" . | 中国细胞生物学学报 45 . 01 (2023) : 122-132 . |
| APA | 余凌奇 , 谢甲钰 , 原垚 , 凌圣安 , 陈文锋 . 利用果蝇模型研究人类Ⅱ型腓骨肌萎缩症的进展 . | 中国细胞生物学学报 , 2023 , 45 (01) , 122-132 . |
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Royal jelly (RJ) is a biologically active substance secreted by the hypopharyngeal and mandibular glands of worker honeybees. It is widely claimed that RJ reduces oxidative stress. However, the antioxidant activity of RJ has mostly been determined by in vitro chemical detection methods or by external administration drugs that cause oxidative stress. Whether RJ can clear the endogenous production of reactive oxygen species (ROS) in cells remains largely unknown. Here, we systematically investigated the antioxidant properties of RJ using several endogenous oxidative stress models of Drosophila. We found that RJ enhanced sleep quality of aging Drosophila, which is decreased due to an increase of oxidative damage with age. RJ supplementation improved survival and suppressed ROS levels in gut cells of flies upon exposure to hydrogen peroxide or to the neurotoxic agent paraquat. Moreover, RJ supplementation moderated levels of ROS in endogenous gut cells and extended lifespan after exposure of flies to heat stress. Sleep deprivation leads to accumulation of ROS in the gut cells, and RJ attenuated the consequences of oxidative stress caused by sleep loss and prolonged lifespan. Mechanistically, RJ prevented cell oxidative damage caused by heat stress or sleep deprivation, with the antioxidant activity in vivo independent of Keap1/Nrf2 signaling. RJ supplementation activated oxidoreductase activity in the guts of flies, suggesting its ability to inhibit endogenous oxidative stress and maintain health, possibly in humans.
Keyword ：
antioxidant antioxidant biological oxidations biological oxidations Drosophila Drosophila oxidative stress oxidative stress royal jelly royal jelly sleep loss sleep loss
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| GB/T 7714 | Wen, Dongjing , Xie, Jiayu , Yuan, Yao et al. The endogenous antioxidant ability of royal jelly in Drosophila is independent of Keap1/Nrf2 by activating oxidoreductase activity [J]. | INSECT SCIENCE , 2023 , 31 (2) : 503-523 . |
| MLA | Wen, Dongjing et al. "The endogenous antioxidant ability of royal jelly in Drosophila is independent of Keap1/Nrf2 by activating oxidoreductase activity" . | INSECT SCIENCE 31 . 2 (2023) : 503-523 . |
| APA | Wen, Dongjing , Xie, Jiayu , Yuan, Yao , Shen, Lirong , Yang, Yufeng , Chen, Wenfeng . The endogenous antioxidant ability of royal jelly in Drosophila is independent of Keap1/Nrf2 by activating oxidoreductase activity . | INSECT SCIENCE , 2023 , 31 (2) , 503-523 . |
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Circadian clocks control the rhythmicity of many behaviors and physiological features of insects. To study the circadian clock of the moth Plutella xylostella, we employed CRISPR/Cas9-mediated genome editing to investigate the effect of loss of the clock gene period on the circadian rhythms. P. xylostella harbors a single copy of period. Phylogenetic analysis showed that P. xylostella PERIOD is more homologous to mouse PERIOD than the PERIOD proteins from bees, flies, mosquitos, and many other Lepidoptera, such as Danaus plexippus and Bombyx mori. The circadian rhythms in adult locomotor activity were altered in the period knockout strain of P. xylostella under light-dark (LD) and continuous dark (DD) conditions. Under the LD cycle, the wild-type moths displayed nocturnal activity with activity peaking very early after lights off and quickly declining after lights on. In contrast, the period knockout strain had no peak in activity when the lights were turned off and exhibited steady activity throughout the hours of darkness. Interestingly, under DD conditions, our results showed that the locomotor rhythm can be maintained without period gene, but at a lower rhythmicity ratio than wild-type. In addition, knockout of period in P. xylostella changed circadian rhythms patterns related to pupal eclosion, mating, egg-laying, and egg hatching. Mechanistically, loss of PERIOD disrupted the molecular rhythm of period and changed the clock transcription rhythm in the heads of the moths under LD and DD conditions. Together, our study indicates that the PERIOD is required for normal expression of many behavioral rhythms in P. xylostella.
Keyword ：
Cas9 Cas9 circadian rhythm circadian rhythm CRISPR CRISPR period period Plutella xylostella Plutella xylostella
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| GB/T 7714 | Wang, Danfeng , Chen, Jing , Yuan, Yao et al. CRISPR/Cas9-mediated knockout of period reveals its function in the circadian rhythms of the diamondback moth Plutella xylostella [J]. | INSECT SCIENCE , 2022 , 30 (3) : 637-649 . |
| MLA | Wang, Danfeng et al. "CRISPR/Cas9-mediated knockout of period reveals its function in the circadian rhythms of the diamondback moth Plutella xylostella" . | INSECT SCIENCE 30 . 3 (2022) : 637-649 . |
| APA | Wang, Danfeng , Chen, Jing , Yuan, Yao , Yu, Lingqi , Yang, Guang , Chen, Wenfeng . CRISPR/Cas9-mediated knockout of period reveals its function in the circadian rhythms of the diamondback moth Plutella xylostella . | INSECT SCIENCE , 2022 , 30 (3) , 637-649 . |
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Objective Despite the increasing number of genes associated with Charcot-Marie-Tooth (CMT) disease, many patients currently still lack appropriate genetic diagnosis for this disease. Autosomal dominant mutations in aminoacyl-tRNA synthetases (ARSs) have been implicated in CMT. Here, we describe causal missense mutations in the gene encoding seryl-tRNA synthetase 1 (SerRS) for 3 families affected with CMT. Methods Whole-exome sequencing was performed in 16 patients and 14 unaffected members of 3 unrelated families. The functional impact of the genetic variants identified was investigated using bioinformatic prediction tools and confirmed using cellular and biochemical assays. Results Combined linkage analysis for the 3 families revealed significant linkage (Zmax LOD = 6.9) between the genomic co-ordinates on chromosome 1: 108681600-110300504. Within the linkage region, heterozygous SerRS missense variants segregated with the clinical phenotype in the 3 families. The mutant SerRS proteins exhibited reduced aminoacylation activity and abnormal SerRS dimerization, which suggests the impairment of total protein synthesis and induction of eIF2 alpha phosphorylation. Interpretation Our findings suggest the heterozygous SerRS variants identified represent a novel cause for autosomal dominant CMT. Mutant SerRS proteins are known to impact various molecular and cellular functions. Our findings provide significant advances on the current understanding of the molecular mechanisms associated with ARS-related CMT. ANN NEUROL 2022
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| GB/T 7714 | He, Jin , Liu, Xiao-Xuan , Ma, Ming-Ming et al. Heterozygous Seryl-tRNA Synthetase 1 Variants Cause Charcot-Marie-Tooth Disease [J]. | ANNALS OF NEUROLOGY , 2022 , 93 (2) : 244-256 . |
| MLA | He, Jin et al. "Heterozygous Seryl-tRNA Synthetase 1 Variants Cause Charcot-Marie-Tooth Disease" . | ANNALS OF NEUROLOGY 93 . 2 (2022) : 244-256 . |
| APA | He, Jin , Liu, Xiao-Xuan , Ma, Ming-Ming , Lin, Jing-Jing , Fu, Jun , Chen, Yi-Kun et al. Heterozygous Seryl-tRNA Synthetase 1 Variants Cause Charcot-Marie-Tooth Disease . | ANNALS OF NEUROLOGY , 2022 , 93 (2) , 244-256 . |
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谷氨酸钠(MSG),也称味精,是谷氨酸的钠盐,也是最丰富的天然存在的非必需氨基酸之一。MSG常作为一种增味剂被添加到食物中,但也有报道可引起哮喘、头痛甚至脑损伤。本文以黑腹果蝇作为材料,利用16S rDNA扩增子测序分析其肠道菌群对高MSG摄入的响应。结果发现饲喂MSG组果蝇相比对照组,其肠道的厚壁杆菌门Firmicutes、芽孢杆菌纲Bacilli、乳杆菌目Lactobacillales、乳杆菌科Lactobacillaceae、乳杆菌属Lactobacillus丰度显著升高。α多样性和β多样性分析也显示饲喂MSG组和对照组的微生物群落组成多样性存在显著差异。该研究证明,高MSG摄入能显著改...
Keyword ：
肠道菌群 肠道菌群 谷氨酸钠 谷氨酸钠 黑腹果蝇 黑腹果蝇
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| GB/T 7714 | 王丹凤 , 谢甲钰 , 杨广 et al. 谷氨酸钠摄入引起的果蝇肠道菌群多样性变化研究 [J]. | 环境昆虫学报 , 2021 , 43 (01) : 170-180 . |
| MLA | 王丹凤 et al. "谷氨酸钠摄入引起的果蝇肠道菌群多样性变化研究" . | 环境昆虫学报 43 . 01 (2021) : 170-180 . |
| APA | 王丹凤 , 谢甲钰 , 杨广 , 陈文锋 . 谷氨酸钠摄入引起的果蝇肠道菌群多样性变化研究 . | 环境昆虫学报 , 2021 , 43 (01) , 170-180 . |
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