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Zebrafish disease modelling

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https://www.readbyqxmd.com/read/28241031/a-novel-early-onset-phenotype-in-a-zebrafish-model-of-merosin-deficient-congenital-muscular-dystrophy
#1
Sarah J Smith, Jeffrey C Wang, Vandana A Gupta, James J Dowling
Merosin deficient congenital muscular dystrophy (MDC1A) is a severe neuromuscular disorder with onset in infancy that is associated with severe morbidities (particularly wheelchair dependence) and early mortality. It is caused by recessive mutations in the LAMA2 gene that encodes a subunit of the extracellular matrix protein laminin 211. At present, there are no treatments for this disabling disease. The zebrafish has emerged as a powerful model system for the identification of novel therapies. However, drug discovery in the zebrafish is largely dependent on the identification of phenotypes suitable for chemical screening...
2017: PloS One
https://www.readbyqxmd.com/read/28224202/germline-specific-dgcr8-knockout-in-zebrafish-using-a-back-approach
#2
Yun Liu, Zeyao Zhu, Idy H T Ho, Yujian Shi, Yuxin Xie, Jianzhen Li, Yong Zhang, Matthew T V Chan, Christopher H K Cheng
Zebrafish is an important model to study developmental biology and human diseases. However, an effective approach to achieve spatial and temporal gene knockout in zebrafish has not been well established. In this study, we have developed a new approach, namely bacterial artificial chromosome-rescue-based knockout (BACK), to achieve conditional gene knockout in zebrafish using the Cre/loxP system. We have successfully deleted the DiGeorge syndrome critical region gene 8 (dgcr8) in zebrafish germ line and demonstrated that the maternal-zygotic dgcr8 (MZdgcr8) embryos exhibit MZdicer-like phenotypes with morphological defects which could be rescued by miR-430, indicating that canonical microRNAs play critical role in early development...
February 21, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28217866/zebrafish-models-in-neuropsychopharmacology-and-cns-drug-discovery
#3
REVIEW
Kanza M Khan, Adam D Collier, Darya A Meshalkina, Elana V Kysil, Sergey L Khatsko, Tatyana Kolesnikova, Yury Yu Morzherin, Jason E Warnick, Allan V Kalueff, David J Echevarria
Despite high prevalence of neuropsychiatric disorders, their etiology and molecular mechanisms remain poorly understood. The zebrafish (Danio rerio) is increasingly utilized as a powerful animal model in neuropharmacology research and in-vivo drug screening. Collectively, this makes zebrafish a useful tool for drug discovery and the identification of disordered molecular pathways. Here, we discuss zebrafish models of selected human neuropsychiatric disorders and drug-induced phenotypes. Covering a broad range of brain disorders (from anxiety and psychoses to neurodegeneration), we also summarize recent developments in zebrafish genetics and small molecule screening, which markedly enhance the disease modeling and the discovery of novel drug targets...
February 20, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28217548/polygonum-multiflorum-root-extract-as-a-potential-candidate-for-treatment-of-early-graying-hair
#4
Nguyen Dinh Thang, Pham Ngoc Diep, Pham Thi Huong Lien, Le Thi Lien
Despite Polygonum multiflorum (PM) has been experiencely used as a drug to treat early graying hair phenomenon in Asian countries for a long time, there is limited study examined the real biological effects of PM on hair graying in vitro and in vivo. In this study, we investigated the effects of PM root extract (PM-RE) on melanin synthesis in human melanoma SKMEL-28 cells and embryos/larvae of wild-type strain AB zebrafish. We also preliminary revealed the molecular mechanism of early hair graying phenomenon in both in vitro and in vivo models...
January 2017: Journal of Advanced Pharmaceutical Technology & Research
https://www.readbyqxmd.com/read/28215820/the-use-of-fish-models-to-study-human-neurological-disorders
#5
Hideaki Matsui
Small teleost fish including zebrafish and medaka have been used as animal models in basic science research due to the relative ease of handling and transparency during embryogenesis. Current advances in genetic engineering and progress in disease genetics allowed utilization of these fish to study neurological diseases and psychiatric disorders. This review summarizes the advantages and disadvantages of using fish for neuropsychiatric research using primarily our own studies as examples. We discuss how fish belong to a class of vertebrates, are feasible for imaging, and include diverse species with multiple research possibilities yet to be discovered...
February 16, 2017: Neuroscience Research
https://www.readbyqxmd.com/read/28215799/comprehensive-understanding-of-pm2-5-on-gene-and-microrna-expression-patterns-in-zebrafish-danio-rerio-model
#6
Junchao Duan, Yang Yu, Yang Li, Li Jing, Man Yang, Ji Wang, Yanbo Li, Xianqing Zhou, Mark R Miller, Zhiwei Sun
PM2.5 is a major public health concern and some severe diseases have been attributed to exposure to PM2.5. However, a comprehensive understanding of gene and microRNA expression patterns induced by PM2.5 is missing. The objective of this study was to evaluate the toxicity of PM2.5 via genome-wide transcriptional analysis in the model teleost fish, zebrafish (Danio rerio). Gene ontology analysis revealed that the most impact gene functional categories induced by PM2.5 included oxidation-reduction process, transport, response to xenobiotic stimulus, response to chemical stimulus and metabolic process...
February 16, 2017: Science of the Total Environment
https://www.readbyqxmd.com/read/28198397/cystinosis-ctns-zebrafish-mutant-shows-pronephric-glomerular-and-tubular-dysfunction
#7
Mohamed A Elmonem, Ramzi Khalil, Ladan Khodaparast, Laleh Khodaparast, Fanny O Arcolino, Joseph Morgan, Anna Pastore, Przemko Tylzanowski, Annelii Ny, Martin Lowe, Peter A de Witte, Hans J Baelde, Lambertus P van den Heuvel, Elena Levtchenko
The human ubiquitous protein cystinosin is responsible for transporting the disulphide amino acid cystine from the lysosomal compartment into the cytosol. In humans, Pathogenic mutations of CTNS lead to defective cystinosin function, intralysosomal cystine accumulation and the development of cystinosis. Kidneys are initially affected with generalized proximal tubular dysfunction (renal Fanconi syndrome), then the disease rapidly affects glomeruli and progresses towards end stage renal failure and multiple organ dysfunction...
February 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28191018/thymosin-%C3%AE-4-improves-differentiation-and-vascularization-of-ehts
#8
Tilman Ziegler, Rabea Hinkel, Andrea Stöhr, Thomas Eschenhagen, Karl-Ludwig Laugwitz, Ferdinand le Noble, Robert David, Arne Hansen, Christian Kupatt
Induced pluripotent stem cells (iPSC) constitute a powerful tool to study cardiac physiology and represents a promising treatment strategy to tackle cardiac disease. However, iPSCs remain relatively immature after differentiation. Additionally, engineered heart tissue (EHT) has been investigated as a therapy option in preclinical disease models with promising results, although their vascularization and functionality leave room for improvement. Thymosin β4 (Tβ4) has been shown to promote the differentiation of progenitor cell lines to cardiomyocytes while it also induces angiogenic sprouting and vascular maturation...
2017: Stem Cells International
https://www.readbyqxmd.com/read/28190554/neuregulin-1-is-involved-in-enteric-nervous-system-development-in-zebrafish
#9
Jiarui Pu, Shaotao Tang, Qiangsong Tong, Guobin Wang, Haibo Jia, Qiong Jia, Kang Li, Dan Li, Dehua Yang, Jun Yang, Hang Li, Shuai Li, Hong Mei
BACKGROUND: Hirschsprung's disease (HD, also known as congenital colon aganglionosis) is a congenital disorder characterized by the absence of intramural ganglion cells in the distal gastrointestinal tract, which results in tonic contraction of the aganglionic gut segment and functional intestinal obstruction. Recent studies have indicated neuregulin 1 (NRG1) as a new candidate gene involved in the development of the enteric nervous system (ENS) in humans. METHODS: In our study, we investigated the role of NRG1 in zebrafish ENS development by assessing NRG1 expression patterns during ENS development...
January 23, 2017: Journal of Pediatric Surgery
https://www.readbyqxmd.com/read/28188734/mixing-and-pumping-functions-of-the-intestine-of-zebrafish-larvae
#10
Jinyou Yang, Yuji Shimogonya, Takuji Ishikawa
Due to its transparency, the intestine of zebrafish larvae has been widely used in studies of gastrointestinal diseases and the microbial flora of the gut. However, transport phenomena in the intestine of zebrafish larvae have not been fully clarified. In this study, therefore, transport caused by peristaltic motion in the intestine of zebrafish larvae was investigated by numerical simulation. An anatomically realistic three-dimensional geometric model of the intestine at various times after feeding was constructed based on the experimental data of Field et al...
February 7, 2017: Journal of Theoretical Biology
https://www.readbyqxmd.com/read/28180938/compound-heterozygous-gata5-mutations-in-a-girl-with-hydrops-fetalis-congenital-heart-defects-and-genital-anomalies
#11
Maja Hempel, Teresa Casar Tena, Thilo Diehl, Martina S Burczyk, Tim M Strom, Christian Kubisch, Melanie Philipp, Davor Lessel
GATA5 belongs to the GATA family of transcription factors characterized by highly evolutionarily conserved zinc-finger DNA-binding domains. Mouse models have implicated a role of GATA5 during mammalian embryogenesis, including proper heart development and gender-specific regulation of female genitourinary tract formation. Previous studies have found an association of heterozygous missense alterations in GATA5 with a broad variety of heart diseases; however, the clinical relevance of the identified susceptibility variants has remained unclear...
February 8, 2017: Human Genetics
https://www.readbyqxmd.com/read/28177980/alzheimer-s-disease-in-the-zebrafish-where-can-we-take-it
#12
Erika M Caramillo, David J Echevarria
With the ever-growing geriatric population, research on brain diseases such as dementia is more imperative now than ever. The most prevalent of all dementias is Alzheimer's disease, a progressive neurodegenerative disease that presents with deficits in memory, cognition, motor skills, and a general decline in the quality of life. The social and economic burden associated with Alzheimer's disease is tremendous and is projected to grow even greater over the coming years. There is a specific need to elucidate and improve the treatments available, not only to alleviate the symptoms related to dementias such as Alzheimer's but also to prevent the formation of the disease...
February 7, 2017: Behavioural Pharmacology
https://www.readbyqxmd.com/read/28173755/melanoma-genome-evolution-across-species
#13
Emily R Kansler, Akanksha Verma, Erin M Langdon, Theresa Simon-Vermot, Alexandra Yin, William Lee, Marc Attiyeh, Olivier Elemento, Richard M White
BACKGROUND: Cancer genomes evolve in both space and time, which contributes to the genetic heterogeneity that underlies tumor progression and drug resistance. In human melanoma, identifying mechanistically important events in tumor evolution is hampered due to the high background mutation rate from ultraviolet (UV) light. Cross-species oncogenomics is a powerful tool for identifying these core events, in which transgenically well-defined animal models of cancer are compared to human cancers to identify key conserved alterations...
February 7, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28167213/metagenomics-approach-to-the-study-of-the-gut-microbiome-structure-and-function-in-zebrafish-danio-rerio-fed-with-gluten-formulated-diet
#14
Hyunmin Koo, Joseph A Hakim, Mickie L Powell, Ranjit Kumar, Peter G Eipers, Casey D Morrow, Michael Crowley, Elliot J Lefkowitz, Stephen A Watts, Asim K Bej
In this study, we report the gut microbial composition and predictive functional profiles of zebrafish, Danio rerio, fed with a control formulated diet (CFD), and a gluten formulated diet (GFD) using a metagenomics approach and bioinformatics tools. The microbial communities of the GFD-fed D. rerio displayed heightened abundances of Legionellales, Rhizobiaceae, and Rhodobacter, as compared to the CFD-fed counterparts. Predicted metagenomics of microbial communities (PICRUSt) in GFD-fed D. rerio showed KEGG functional categories corresponding to bile secretion, secondary bile acid biosynthesis, and the metabolism of glycine, serine, and threonine...
February 3, 2017: Journal of Microbiological Methods
https://www.readbyqxmd.com/read/28157230/conserved-gene-regulation-during-acute-inflammation-between-zebrafish-and-mammals
#15
G Forn-Cuní, M Varela, P Pereiro, B Novoa, A Figueras
Zebrafish (Danio rerio), largely used as a model for studying developmental processes, has also emerged as a valuable system for modelling human inflammatory diseases. However, in a context where even mice have been questioned as a valid model for these analysis, a systematic study evaluating the reproducibility of human and mammalian inflammatory diseases in zebrafish is still lacking. In this report, we characterize the transcriptomic regulation to lipopolysaccharide in adult zebrafish kidney, liver, and muscle tissues using microarrays and demonstrate how the zebrafish genomic responses can effectively reproduce the mammalian inflammatory process induced by acute endotoxin stress...
February 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28148893/stem-cell-cultures-derived-from-pediatric-brain-tumors-accurately-model-the-originating-tumors
#16
Anna Wenger, Susanna Larsson, Anna Danielsson, Kirstine Juul Elbæk, Petronella Kettunen, Magnus Tisell, Magnus Sabel, Birgitta Lannering, Claes Nordborg, Elizabeth Schepke, Helena Carén
Brain tumors are the leading cause of cancer-related death in children but high-grade gliomas in children and adolescents have remained a relatively under-investigated disease despite this. A better understanding of the cellular and molecular pathogenesis of the diseases is required in order to improve the outcome for these children. In vitro-cultured primary tumor cells from patients are indispensable tools for this purpose by enabling functional analyses and development of new therapies. However, relevant well-characterized in vitro cultures from pediatric gliomas cultured under serum-free conditions have been lacking...
January 26, 2017: Oncotarget
https://www.readbyqxmd.com/read/28148768/variation-in-wall-shear-stress-in-channel-networks-of-zebrafish-models
#17
Woorak Choi, Hye Mi Kim, Sungho Park, Eunseop Yeom, Junsang Doh, Sang Joon Lee
Physiological functions of vascular endothelial cells (ECs) vary depending on wall shear stress (WSS) magnitude, and the functional change affects the pathologies of various cardiovascular systems. Several in vitro and in vivo models have been used to investigate the functions of ECs under different WSS conditions. However, these models have technical limitations in precisely mimicking the physiological environments of ECs and monitoring temporal variations of ECs in detail. Although zebrafish (Danio rerio) has several strategies to overcome these technical limitations, zebrafish cannot be used as a perfect animal model because applying various WSS conditions on blood vessels of zebrafish is difficult...
February 2017: Journal of the Royal Society, Interface
https://www.readbyqxmd.com/read/28148530/usp40-gene-knockdown-disrupts-glomerular-permeability-in-zebrafish
#18
Hisashi Takagi, Yukino Nishibori, Kan Katayama, Tomohisa Katada, Shohei Takahashi, Zentaro Kiuchi, Shin-Ichiro Takahashi, Hiroyasu Kamei, Hayato Kawakami, Yoshihiro Akimoto, Akihiko Kudo, Katsuhiko Asanuma, Hiromu Takematsu, Kunimasa Yan
Unbiased transcriptome profiling and functional genomics approaches have identified ubiquitin specific protease 40 (USP40) as a highly specific glomerular transcript. This gene product remains uncharacterized, and its biological function is completely unknown. Here, we showed that mouse and rat glomeruli exhibit specific expression of the USP40 protein, which migrated at 150 kDa and was exclusively localized in the podocyte cytoplasm of the adult kidney. Double-labeling immunofluorescence staining and confocal microscopy analysis of fetal and neonate kidney samples revealed that USP40 was also expressed in the vasculature, including in glomerular endothelial cells at the premature stage...
February 1, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28141764/crispr-applications-in-ophthalmologic-genome-surgery
#19
Thiago Cabral, James E DiCarlo, Sally Justus, Jesse D Sengillo, Yu Xu, Stephen H Tsang
PURPOSE OF REVIEW: The present review seeks to summarize and discuss the application of clustered regularly interspaced short palindromic repeats (CRISPR)-associated systems (Cas) for genome editing, also called genome surgery, in the field of ophthalmology. RECENT FINDINGS: Precision medicine is an emerging approach for disease treatment and prevention that takes into account the variability of an individual's genetic sequence. Various groups have used CRISPR-Cas genome editing to make significant progress in mammalian preclinical models of eye disease, the basic science of eye development in zebrafish, the in vivo modification of ocular tissue, and the correction of stem cells with therapeutic applications...
January 30, 2017: Current Opinion in Ophthalmology
https://www.readbyqxmd.com/read/28137359/pharmacological-targeting-of-the-transcription-factor-sox18-delays-breast-cancer-in-mice
#20
Jeroen Overman, Frank Fontaine, Mehdi Moustaqil, Deepak Mittal, Emma Sierecki, Natalia Sacilotto, Johannes Zuegg, Avril Ab Robertson, Kelly Holmes, Angela A Salim, Sreeman Mamidyala, Mark S Butler, Ashley S Robinson, Emmanuelle Lesieur, Wayne Johnston, Kirill Alexandrov, Brian L Black, Benjamin M Hogan, Sarah De Val, Robert J Capon, Jason S Carroll, Timothy L Bailey, Peter Koopman, Ralf Jauch, Mark J Smyth, Matthew A Cooper, Yann Gambin, Mathias Francois
Pharmacological targeting of transcription factors holds great promise for the development of new therapeutics, but strategies based on blockade of DNA binding, nuclear shuttling, or individual protein partner recruitment have yielded limited success to date. Transcription factors typically engage in complex interaction networks, likely masking the effects of specifically inhibiting single protein-protein interactions. Here, we used a combination of genomic, proteomic and biophysical methods to discover a suite of protein-protein interactions involving the SOX18 transcription factor, a known regulator of vascular development and disease...
31, 2017: ELife
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