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CRISPR AND animal Models

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https://www.readbyqxmd.com/read/30117419/-progress-and-application-of-genome-edited-pigs-in-biomedical-research
#1
Yao Qiang Huang, Guo Ling Li, Hua Qiang Yang, Zhen Fang Wu
Genome editing technologies (GETs) can precisely alter the genomic sequences and modify the genetic information at the target site of an organism. Since the beginning of the 21st century, the GETs, including zinc finger nucleases (ZFN), transcription-activating-like receptor factor (TALEN), and clustered regularly interspaced short palindromic repeats/Cas endonucleases (CRISPR/Cas), have been successively developed. The GETs can easily engineer the targeted genomic site of animals to exhibit a desired phenotype(s), thereby providing valuable tools in biomedical research...
August 16, 2018: Yi Chuan, Hereditas
https://www.readbyqxmd.com/read/30111571/infection-dynamics-of-hepatitis-e-virus-in-wild-type-and-immunoglobulin-heavy-chain-knockout-j-h-gnotobiotic-piglets
#2
Danielle M Yugo, C Lynn Heffron, Junghyun Ryu, Kyungjun Uh, Sakthivel Subramaniam, Shannon R Matzinger, Christopher Overend, Dianjun Cao, Scott P Kenney, Harini Sooryanarain, Thomas Cecere, Tanya LeRoith, Lijuan Yuan, Nathaniel Jue, Sherrie Clark-Deener, Kiho Lee, Xiang-Jin Meng
Hepatitis E virus (HEV), the causative agent of hepatitis E, is an important but incompletely understood pathogen causing high mortality during pregnancy and leading to chronic hepatitis in immunocompromised individuals. The underlying mechanisms leading to hepatic damage remain unknown; however, the humoral immune response is implicated. In this study, immunoglobulin (Ig) heavy chain JH (-/-) knockout gnotobiotic pigs were generated using CRISPR/Cas9 technology to deplete the B-lymphocyte population resulting in an inability to generate a humoral immune response to genotype 3 HEV infection...
August 15, 2018: Journal of Virology
https://www.readbyqxmd.com/read/30090702/combining-genotypic-and-phenotypic-analyses-on-single-mutant-zebrafish-larvae
#3
Barbara Dupret, Pamela Völkel, Pauline Follet, Xuefen Le Bourhis, Pierre-Olivier Angrand
Zebrafish is a powerful animal model used to study vertebrate embryogenesis, organ development and diseases (Gut et al., 2017) [1]. The usefulness of the model was established as a result of various large forward genetic screens identifying mutants in almost every organ or cell type (Driever et al., 1996; Haffter et al., 1996) [[2], [3]]. More recently, the advent of genome editing methodologies, including TALENs (Sander et al., 2011) [4] and the CRISPR/Cas9 technology (Hwang et al., 2013) [5], led to an increase in the production of zebrafish mutants...
2018: MethodsX
https://www.readbyqxmd.com/read/30090689/the-potential-of-crispr-cas9-gene-editing-as-a-treatment-strategy-for-alzheimer-s-disease
#4
Troy T Rohn, Nayoung Kim, Noail F Isho, Jacob M Mack
Despite a wealth of knowledge gained in the past three decades concerning the molecular underpinnings of Alzheimer's disease (AD), progress towards obtaining effective, disease modifying therapies has proven to be challenging. In this manner, numerous clinical trials targeting the production, aggregation, and toxicity of beta-amyloid, have failed to meet efficacy standards. This puts into question the beta-amyloid hypothesis and suggests that additional treatment strategies should be explored. The recent emergence of CRISPR/Cas9 gene editing as a relatively straightforward, inexpensive, and precise system has led to an increased interest of applying this technique in AD...
2018: Journal of Alzheimer's Disease and Parkinsonism
https://www.readbyqxmd.com/read/30089813/precision-gene-editing-technology-and-applications-in-nephrology
#5
REVIEW
Zachary WareJoncas, Jarryd M Campbell, Gabriel Martínez-Gálvez, William A C Gendron, Michael A Barry, Peter C Harris, Caroline R Sussman, Stephen C Ekker
The expanding field of precision gene editing is empowering researchers to directly modify DNA. Gene editing is made possible using synonymous technologies: a DNA-binding platform to molecularly locate user-selected genomic sequences and an associated biochemical activity that serves as a functional editor. The advent of accessible DNA-targeting molecular systems, such as zinc-finger nucleases, transcription activator-like effectors (TALEs) and CRISPR-Cas9 gene editing systems, has unlocked the ability to target nearly any DNA sequence with nucleotide-level precision...
August 8, 2018: Nature Reviews. Nephrology
https://www.readbyqxmd.com/read/30089727/cardiovascular-consequences-of-katp-overactivity-in-cantu-syndrome
#6
Yan Huang, Conor McClenaghan, Theresa M Harter, Kristina Hinman, Carmen M Halabi, Scot J Matkovich, Haixia Zhang, G Schuyler Brown, Robert P Mecham, Sarah K England, Attila Kovacs, Maria S Remedi, Colin G Nichols
Cantu syndrome (CS) is characterized by multiple vascular and cardiac abnormalities including vascular dilation and tortuosity, systemic hypotension, and cardiomegaly. The disorder is caused by gain-of-function (GOF) mutations in genes encoding pore-forming (Kir6.1, KCNJ8) and accessory (SUR2, ABCC9) ATP-sensitive potassium (KATP) channel subunits. However, there is little understanding of the link between molecular dysfunction and the complex pathophysiology observed, and there is no known treatment, in large part due to the lack of appropriate preclinical disease models in which to test therapies...
August 9, 2018: JCI Insight
https://www.readbyqxmd.com/read/30085885/disruption-of-g-0-g-1-switch-gene-2-g0s2-reduced-abdominal-fat-deposition-and-altered-fatty-acid-composition-in-chicken
#7
Tae Sub Park, Joonghoon Park, Jeong Hyo Lee, Jeong-Woong Park, Byung-Chul Park
Chicken as a food source is one of the most widespread domestic animals, and it has been used extensively as a research model. The clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein 9 (Cas9) system is the most efficient and reliable tool for precise genome-targeted modification and has generated considerable excitement for industrial applications, as well as biologic science. Unlike in mammals, germline-transmittable primordial germ cells (PGCs) in chicken were used as an alternative strategy for the production of genetically altered chickens...
August 7, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/30077989/gene-editing-for-inflammatory-disorders
#8
REVIEW
David T Ewart, Erik J Peterson, Clifford J Steer
Technology for precise and efficient genetic editing is constantly evolving and is now capable of human clinical applications. Autoimmune and inflammatory diseases are chronic, disabling, sometimes life-threatening, conditions that feature heritable components. Both primary genetic lesions and the inflammatory pathobiology underlying these diseases represent fertile soil for new therapies based on the capabilities of gene editing. The ability to orchestrate precise targeted modifications to the genome will likely enable cell-based therapies for inflammatory diseases such as monogenic autoinflammatory disease, acquired autoimmune disease and for regenerative medicine in the setting of an inflammatory environment...
August 4, 2018: Annals of the Rheumatic Diseases
https://www.readbyqxmd.com/read/30076892/fishing-for-understanding-unlocking-the-zebrafish-gene-editor-s-toolbox
#9
REVIEW
Brandon W Simone, Gabriel Martínez-Gálvez, Zachary WareJoncas, Stephen C Ekker
The rapid growth of the field of gene editing can largely be attributed to the discovery and optimization of designer endonucleases. These include zinc finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs), and clustered regular interspersed short palindromic repeat (CRISPR) systems including Cas9, Cas12a, and structure-guided nucleases. Zebrafish (Danio rerio) have proven to be a powerful model system for genome engineering testing and applications due to their external development, high fecundity, and ease of housing...
August 2, 2018: Methods: a Companion to Methods in Enzymology
https://www.readbyqxmd.com/read/30076839/chymotrypsin-reduces-the-severity-of-secretagogue-induced-pancreatitis-in-mice
#10
Zsanett Jancsó, Eszter Hegyi, Miklós Sahin-Tóth
Intra-pancreatic activation of the digestive proteases trypsin and chymotrypsin is an early event in the development of pancreatitis. Human genetic studies indicate that chymotrypsin controls trypsin activity via degradation, but there is no evidence of this from animal models. We used CRISPR-Cas9 to disrupt the chymotrypsinogen B1 gene (Ctrb1) in C57BL/6N mice and induced pancreatitis in CTRB1-deficient and C57BL/6N (control) mice by administration of cerulein. CTRB1-deficient mice given cerulein had significant increases in intra-pancreatic trypsin activity and developed more severe pancreatitis compared with control mice...
August 1, 2018: Gastroenterology
https://www.readbyqxmd.com/read/30075130/gfap-mutations-in-astrocytes-impair-oligodendrocyte-progenitor-proliferation-and-myelination-in-an-hipsc-model-of-alexander-disease
#11
Li Li, E Tian, Xianwei Chen, Jianfei Chao, Jeremy Klein, Qiuhao Qu, Guihua Sun, Guoqiang Sun, Yanzhou Huang, Charles D Warden, Peng Ye, Lizhao Feng, Xinqiang Li, Qi Cui, Abdullah Sultan, Panagiotis Douvaras, Valentina Fossati, Neville E Sanjana, Arthur D Riggs, Yanhong Shi
Alexander disease (AxD) is a leukodystrophy that primarily affects astrocytes and is caused by mutations in the astrocytic filament gene GFAP. While astrocytes are thought to have important roles in controlling myelination, AxD animal models do not recapitulate critical myelination phenotypes and it is therefore not clear how AxD astrocytes contribute to leukodystrophy. Here, we show that AxD patient iPSC-derived astrocytes recapitulate key features of AxD pathology such as GFAP aggregation. Moreover, AxD astrocytes inhibit proliferation of human iPSC-derived oligodendrocyte progenitor cells (OPCs) in co-culture and reduce their myelination potential...
August 2, 2018: Cell Stem Cell
https://www.readbyqxmd.com/read/30065072/use-of-zebrafish-models-to-investigate-rare-human-disease
#12
Kathryn Isabel Adamson, Eamonn Sheridan, Andrew James Grierson
Rare diseases are collectively common and often extremely debilitating. Following the emergence of next-generation sequencing (NGS) technologies, the variants underpinning rare genetic disorders are being unearthed at an accelerating rate. However, many rare conditions lack effective treatments due to their poorly understood pathophysiology. There is therefore a growing demand for the development of novel experimental models of rare genetic diseases, so that potentially causative variants can be validated, pathogenic mechanisms can be investigated and therapeutic targets can be identified...
July 31, 2018: Journal of Medical Genetics
https://www.readbyqxmd.com/read/30065043/parallel-genomic-engineering-of-two-drosophila-genes-using-orthogonal-attb-attp-sites
#13
Beatriz Blanco-Redondo, Tobias Langenhan
Precise modification of sequences in the Drosophila melanogaster genome underlies the powerful capacity to study molecular structure-function relationships in this model species. The emergence of CRISPR/Cas9 tools in combination with recombinase systems such as the bacteriophage serine integrase ΦC31 has rendered Drosophila mutagenesis a straightforward enterprise for deleting, inserting and modifying genetic elements to study their functional relevance. However, while combined modifications of non-linked genetic elements can be easily constructed with these tools and classical genetics, the independent manipulation of linked genes through the established ΦC31-mediated transgenesis pipeline has not been feasible due to the limitation to one attB/attP site pair...
July 31, 2018: G3: Genes—Genomes—Genetics
https://www.readbyqxmd.com/read/30061297/cancer-modeling-by-transgene-electroporation-in-adult-zebrafish-teaz
#14
Scott J Callahan, Stephanie Tepan, Yan M Zhang, Helen Lindsay, Alexa Burger, Nathaniel R Campbell, Isabella S Kim, Travis J Hollmann, Lorenz Studer, Christian Mosimann, Richard M White
Transgenic animals are invaluable for modeling cancer genomics, but often require complex crosses of multiple germline alleles to obtain the desired combinations. Zebrafish models have advantages in that transgenes can be rapidly tested by mosaic expression, but these typically lack spatial and temporal control of tumor onset, which limits their utility for the study of tumor progression and metastasis. To overcome these limitations, we have developed a method called Transgene Electroporation in Adult Zebrafish (TEAZ)...
July 30, 2018: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/30043366/using-crispr-cas9-system-to-introduce-targeted-mutation-in-arabidopsis
#15
Ze Hong Lee, Nobutoshi Yamaguchi, Toshiro Ito
Gene editing enables the modification of genetic information in a targeted manner. Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) is a gene editing approach that has been widely used in both the animal and plant studies. Plant transcription factors play critical roles in plant development. Recent studies have used the CRISPER/Cas9 system to disrupt transcription factors and cis-elements in plants. In this chapter, we describe a protocol of using the CRISPR/Cas9 system to generate transcription factor mutants in the model plant species Arabidopsis thaliana...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/30042186/xrcc2-mutation-causes-meiotic-arrest-azoospermia-and-infertility
#16
Yongjia Yang, Jihong Guo, Lei Dai, Yimin Zhu, Hao Hu, Lihong Tan, Weijian Chen, Desheng Liang, Jingliang He, Ming Tu, Kewei Wang, Lingqian Wu
BACKGROUND: Meiotic homologous recombination (HR) plays an essential role in gametogenesis. In most eukaryotes, meiotic HR is mediated by two recombinase systems: ubiquitous RAD51 and meiosis-specific DMC1. In the RAD51-mediated HR system, RAD51 and five RAD51 paralogues are essential for normal RAD51 function, but the role of RAD51 in human meiosis is unclear. The knockout of Rad51 or any Rad51 paralogue in mice exhibits embryonic lethality. We investigated a family with meiotic arrest, azoospermia and infertility but without other abnormalities...
July 24, 2018: Journal of Medical Genetics
https://www.readbyqxmd.com/read/30042156/crispr-cas9-mediated-angptl8-knockout-suppresses-plasma-triglyceride-concentrations-and-adiposity-in-rats
#17
Ryota Izumi, Toru Kusakabe, Michio Noguchi, Hiroshi Iwakura, Tomohiro Tanaka, Takashi Miyazawa, Daisuke Aotani, Kiminori Hosoda, Kenji Kangawa, Kazuwa Nakao
Angiopoietin-like protein 8 (ANGPTL8) is a liver- and adipocyte-derived protein that controls plasma TG levels. Most animal studies have used mouse models. Here, we generated an Angptl8 knockout (KO) rat model using a CRISPR/Cas9 system to clarify the roles of ANGPTL8 in glucose and lipid metabolism. Compared with wild-type (WT) rats, Angptl8 KO rats had lower body weight and fat content, associated with impaired lipogenesis in adipocytes; no differences existed between the groups in food intake or rectal temperature...
July 24, 2018: Journal of Lipid Research
https://www.readbyqxmd.com/read/30032995/monitoring-ecdysteroid-activities-using-genetically-encoded-reporter-gene-in-daphnia-magna
#18
Nikko Adhitama, Tomoaki Matsuura, Yasuhiko Kato, Hajime Watanabe
Ecdysteroid is an important hormone that regulates growth, reproduction, and embryogenesis in arthropods. However, little is known about its role and action mechanism in crustaceans, despite their pivotal role in aquatic ecosystem. Daphnia magna, a freshwater crustacean, is used as a classic model organism in ecology and ecotoxicology. Its ecdysteroid activity has been partially characterized previously. However, the spatio-temporal behavior of ecdysteroid, especially during early embryogenesis, when it is thought to have pivotal roles, is still unclear...
July 11, 2018: Marine Environmental Research
https://www.readbyqxmd.com/read/30031067/gene-profile-of-zebrafish-fin-regeneration-offers-clues-to-kinetics-organization-and-biomechanics-of-basement-membrane
#19
Pauline Nauroy, Alexandre Guiraud, Julien Chlasta, Marilyne Malbouyres, Benjamin Gillet, Sandrine Hughes, Elise Lambert, Florence Ruggiero
How some animals regenerate missing body parts is not well understood. Taking advantage of the zebrafish caudal fin model, we performed a global unbiased time-course transcriptomic analysis of fin regeneration. Biostatistics analyses identified extracellular matrix (ECM) as the most enriched gene sets. Basement membranes (BMs) are specialized ECM structures that provide tissues with structural cohesion and serve as a major extracellular signaling platform. While the embryonic formation of BM has been extensively investigated, its regeneration in adults remains poorly studied...
July 19, 2018: Matrix Biology: Journal of the International Society for Matrix Biology
https://www.readbyqxmd.com/read/30027767/crispr-cas9-therapies-in-experimental-mouse-models-of-cancer
#20
Diogo Estêvão, Natália Rios Costa, Rui Gil da Costa, Rui Medeiros
The CRISPR-Cas9, a part of the defence mechanism from bacteria, has rapidly become the simplest, fastest and the most precise genome-editing tool available. The therapeutic applications of CRISPR are boundless: correction of mutations in several disorders, inactivation of oncogenes and viral oncoproteins, and activation of tumor suppressor genes. In this review, we expose recent advances concerning animal models of cancer that use CRISPR-Cas9, addressing also the current efforts to develop CRISPR-Cas9-based therapies, focusing on proof-of-concept studies...
July 20, 2018: Future Oncology
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