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https://www.readbyqxmd.com/read/28815851/basics-of-genome-editing-technology-and-its-application-in-livestock-species
#1
REVIEW
Bjoern Petersen
In the last decade, the research community has witnessed a blooming of targeted genome editing tools and applications. Novel programmable DNA nucleases such as zinc finger nucleases (ZFNs), transcription activator-like endonucleases (TALENs) and the clustered regularly interspaced short palindromic repeats/Cas9 system (CRISPR/Cas9) possess long recognition sites and are capable of cutting DNA in a very specific manner. These DNA nucleases mediate targeted genetic alterations by enhancing the DNA mutation rate via induction of double-strand breaks at a predetermined genomic site...
August 2017: Reproduction in Domestic Animals, Zuchthygiene
https://www.readbyqxmd.com/read/28815495/ligand-controlled-site-specific-recombination-in-zebrafish
#2
Avinash Chekuru, Veronika Kuscha, Stefan Hans, Michael Brand
Cre-mediated site-specific recombination has emerged as an indispensable tool for the precise manipulation of genomes allowing lineage-tracing studies, temporal and spatial misexpressions, and in particular the generation of conditional knockout alleles. Previously, we and others showed that Cre and its ligand-inducible variant CreER(T2) are also highly efficient in the developing and adult zebrafish. The number of Cre driver and effector lines is currently still limited in zebrafish. However, the recent advent of novel genome editing tools such as TALEN and CRISPR/Cas will significantly increase interest in the conditional Cre/lox-technology in this organism...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28810059/targeted-genome-editing-in-caenorhabditis-elegans-using-crispr-cas9
#3
REVIEW
Behnom Farboud
Utilization of programmable nucleases to generate DNA lesions at precise endogenous sequences has transformed the ability to edit genomes from microbes to plants and animals. This is especially true in organisms that previously lacked the means to engineer precise genomic changes, like Caenorhabditis elegans. C. elegans is a 1 mm long free-living, nonparasitic, nematode worm, which is easily cultivated in a laboratory. Its detailed genetic map and relatively compact genome (~100 megabases) helped make it the first metazoan to have its entire genome sequenced...
August 15, 2017: Wiley Interdisciplinary Reviews. Developmental Biology
https://www.readbyqxmd.com/read/28800419/genome-editing-and-plant-transformation-of-solanaceous-food-crops
#4
REVIEW
Joyce Van Eck
During the past decade, the ability to alter plant genomes in a DNA site-specific manner was realized through availability of sequenced genomes and emergence of editing technologies based on complexes that guide endonucleases. Generation of targeted DNA breaks by ZFNs, TALENs, and CRISPR/Cas9, then mending by repair mechanisms, provides a valuable foundation for studies of gene function and trait modification. Genome editing has been successful in several food crops, including those belonging to the Solanaceae, which contains some of the most widely used, economically important ones such as tomato and potato...
August 8, 2017: Current Opinion in Biotechnology
https://www.readbyqxmd.com/read/28782810/establishment-of-estrogen-receptor-1-esr1-knockout-medaka-esr1-is-dispensable-for-sexual-development-and-reproduction-in-medaka-oryzias-latipes
#5
Saki Tohyama, Yukiko Ogino, Anke Lange, Taijun Myosho, Tohru Kobayashi, Yu Hirano, Gen Yamada, Tomomi Sato, Norihisa Tatarazako, Charles R Tyler, Taisen Iguchi, Shinichi Miyagawa
Estrogens play fundamental roles in regulating reproductive activities and they act through estrogen receptor (ESR) in all vertebrates. Most vertebrates have two ESR subtypes (ESR1 and ESR2), whereas teleost fish have at least three (Esr1, Esr2a and Esr2b). Intricate functionalization has been suggested among the Esr subtypes, but to date, distinct roles of Esr have been characterized in only a limited number of species. Study of loss-of-function in animal models is a powerful tool for application to understanding vertebrate reproductive biology...
August 7, 2017: Development, Growth & Differentiation
https://www.readbyqxmd.com/read/28782493/big-data-and-genome-editing-technology-a-new-paradigm-of-cardiovascular-genomics
#6
Chayakrit Krittanawong, Tao Sun, Eyal Herzog
Cardiovascular diseases (CVDs) encompasse a range of conditions extending from congenital heart disease to acute coronary syndrome most of which are heterogenous in nature and some of them are multiple genetic loci. However, the pathogenesis of most CVDs remains incompletely understood. The advance in genome-editing technologies, an engineering process of DNA sequences at precise genomic locations, has enabled a new paradigm that human genome can be precisely modified to achieve a therapeutic effect. Genome-editing includes the correction of genetic variants that cause disease, the addition of therapeutic genes to specific sites in the genomic locations, and the removal of deleterious genes or genome sequences...
August 4, 2017: Current Cardiology Reviews
https://www.readbyqxmd.com/read/28777806/claudin-4-knockout-by-talen-mediated-gene-targeting-in-mdck-cells-claudin-4-is-dispensable-for-the-permeability-properties-of-tight-junctions-in-wild-type-mdck-cells
#7
Shinsaku Tokuda, Toyohiro Hirai, Mikio Furuse
Epithelia act as a barrier between the internal and external environments, and the movement of substances via the paracellular pathway is regulated by tight junctions (TJs). Claudins are major determinants of TJ permeability. Claudin-4 was the first claudin whose involvement in the TJ permeability in cultured cells was directly demonstrated, but the permeability properties of individual claudins including claudin-4 are still incompletely clarified. In this study, we established claudin-4 knockout cells using transcription activator-like effector nucleases (TALENs), a recently developed method for genome editing, and investigated the permeability property of claudin-4 in MDCK II cells...
2017: PloS One
https://www.readbyqxmd.com/read/28767718/zygotic-vinculin-is-not-essential-for-embryonic-development-in-zebrafish
#8
Mitchell K L Han, Gerard N M van der Krogt, Johan de Rooij
The formation of multicellular tissues during development is governed by mechanical forces that drive cell shape and tissue architecture. Protein complexes at sites of adhesion to the extracellular matrix (ECM) and cell neighbors, not only transmit these mechanical forces, but also allow cells to respond to changes in force by inducing biochemical feedback pathways. Such force-induced signaling processes are termed mechanotransduction. Vinculin is a central protein in mechanotransduction that in both integrin-mediated cell-ECM and cadherin-mediated cell-cell adhesions mediates force-induced cytoskeletal remodeling and adhesion strengthening...
2017: PloS One
https://www.readbyqxmd.com/read/28765827/traceless-targeting-and-isolation-of-gene-edited-immortalized-keratinocytes-from-epidermolysis-bullosa-simplex-patients
#9
Magomet Aushev, Ulrich Koller, Claudio Mussolino, Toni Cathomen, Julia Reichelt
Epidermolysis bullosa simplex (EBS) is a blistering skin disease caused by dominant-negative mutations in either KRT5 or KRT14, resulting in impairment of keratin filament structure and epidermal fragility. Currently, nearly 200 mutations distributed across the entire length of these genes are known to cause EBS. Genome editing using programmable nucleases enables the development of ex vivo gene therapies for dominant-negative genetic diseases. A clinically feasible strategy involves the disruption of the mutant allele while leaving the wild-type allele unaffected...
September 15, 2017: Molecular Therapy. Methods & Clinical Development
https://www.readbyqxmd.com/read/28764765/late-phase-immune-responses-limiting-oocyst-survival-are-independent-of-tep1-function-yet-display-strain-specific-differences-in-anopheles-gambiae
#10
Hyeogsun Kwon, Benjamin R Arends, Ryan C Smith
BACKGROUND: There is emerging evidence that mosquito anti-Plasmodium immunity is multimodal with distinct mechanisms for killing malaria parasites at either the ookinete or oocyst stages. Early-phase responses targeting the ookinete require complement-like components circulating in the mosquito hemolymph that result in TEP1-mediated lysis or melanization. Additional responses mediated by the LL3 and STAT pathways limit oocyst survival through unknown mechanisms that require mosquito hemocyte function...
August 1, 2017: Parasites & Vectors
https://www.readbyqxmd.com/read/28763675/transcriptional-and-epigenetic-control-in-mouse-pluripotency-lessons-from-in-vivo-and-in-vitro-studies
#11
REVIEW
Ehsan Habibi, Hendrik G Stunnenberg
Pluripotent cells were first derived from mouse blastocysts several decades ago. Since then, our knowledge of the molecular events that occur in the pre-implantation embryo has been vastly progressing. The emergence of epigenetics has revolutionized stem cell and developmental biology and further deepened our understanding of the underlying molecular mechanisms controlling the early embryo development. In particular, the emergence of massive parallel sequencing technologies has opened new avenues and became indispensable tools in modern biology...
July 29, 2017: Current Opinion in Genetics & Development
https://www.readbyqxmd.com/read/28755320/evaluation-of-the-mature-grain-phytase-candidate-hvpaphy_a-gene-in-barley-hordeum-vulgare-l-using-crispr-cas9-and-talens
#12
Inger B Holme, Toni Wendt, Javier Gil-Humanes, Lise C Deleuran, Colby G Starker, Daniel F Voytas, Henrik Brinch-Pedersen
In the present study, we utilized TALEN- and CRISPR/Cas9-induced mutations to analyze the promoter of the barley phytase gene HvPAPhy_a. The purpose of the study was dual, validation of the PAPhy_a enzyme as the main contributor of the mature grain phytase activity (MGPA), as well as validating the importance of a specific promoter region of the PAPhy_a gene which contains three overlapping cis-acting regulatory elements (GCN4, Skn1 and the RY-element) known to be involved in gene expression during grain filling...
July 28, 2017: Plant Molecular Biology
https://www.readbyqxmd.com/read/28753586/development-of-zebrafish-medulloblastoma-like-pnet-model-by-talen-mediated-somatic-gene-inactivation
#13
Jaegal Shim, Jung-Hwa Choi, Moon-Hak Park, Hyena Kim, Jong Hwan Kim, Seon-Young Kim, Dongwan Hong, Sunshin Kim, Ji Eun Lee, Cheol-Hee Kim, Jeong-Soo Lee, Young-Ki Bae
Genetically engineered animal tumor models have traditionally been generated by the gain of single or multiple oncogenes or the loss of tumor suppressor genes; however, the development of live animal models has been difficult given that cancer phenotypes are generally induced by somatic mutation rather than by germline genetic inactivation. In this study, we developed somatically mutated tumor models using TALEN-mediated somatic gene inactivation of cdkn2a/b or rb1 tumor suppressor genes in zebrafish. One-cell stage injection of cdkn2a/b-TALEN mRNA resulted in malignant peripheral nerve sheath tumors with high frequency (about 39%) and early onset (about 35 weeks of age) in F0 tp53e7/e7 mutant zebrafish...
July 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/28750036/generation-and-phenotypic-characterization-of-pde1a-mutant-mice
#14
Xiaofang Wang, Satsuki Yamada, Wells B LaRiviere, Hong Ye, Jason L Bakeberg, María V Irazabal, Fouad T Chebib, Jan van Deursen, Peter C Harris, Caroline R Sussman, Atta Behfar, Christopher J Ward, Vicente E Torres
It has been proposed that a reduction in intracellular calcium causes an increase in intracellular cAMP and PKA activity through stimulation of calcium inhibitable adenylyl cyclase 6 and inhibition of phosphodiesterase 1 (PDE1), the main enzymes generating and degrading cAMP in the distal nephron and collecting duct, thus contributing to the development and progression of autosomal dominant polycystic kidney disease (ADPKD). In zebrafish pde1a depletion aggravates and overexpression ameliorates the cystic phenotype...
2017: PloS One
https://www.readbyqxmd.com/read/28732771/application-of-the-gene-editing-tool-crispr-cas9-for-treating-neurodegenerative-diseases
#15
REVIEW
Nivya Kolli, Ming Lu, Panchanan Maiti, Julien Rossignol, Gary Leo Dunbar
Increased accumulation of transcribed protein from the damaged DNA and reduced DNA repair capability contributes to numerous neurological diseases for which effective treatments are lacking. Gene editing techniques provide new hope for replacing defective genes and DNA associated with neurological diseases. With advancements in using such editing tools as zinc finger nucleases (ZFNs), meganucleases, and transcription activator-like effector nucleases (TALENs), etc., scientists are able to design DNA-binding proteins, which can make precise double-strand breaks (DSBs) at the target DNA...
July 18, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28729031/knockout-of-the-urate-oxidase-gene-provides-a-stable-mouse-model-of-hyperuricemia-associated-with-metabolic-disorders
#16
Jie Lu, Xu Hou, Xuan Yuan, Lingling Cui, Zhen Liu, Xinde Li, Lidan Ma, Xiaoyu Cheng, Ying Xin, Can Wang, Keke Zhang, Xuefeng Wang, Wei Ren, Ruixia Sun, Zhaotong Jia, Zibin Tian, Qing-Sheng Mi, Changgui Li
The urate oxidase (Uox) gene encodes uricase that in the rodent liver degrades uric acid into allantoin, forming an obstacle for establishing stable mouse models of hyperuricemia. The loss of uricase in humans during primate evolution causes their vulnerability to hyperuricemia. Thus, we generated a Uox-knockout mouse model on a pure C57BL/6J background using the transcription activator-like effector nuclease (TALEN) technique. These Uox-knockout mice spontaneously developed hyperuricemia (over 420 μmol/l) with about 40% survival up to 62 weeks...
July 17, 2017: Kidney International
https://www.readbyqxmd.com/read/28714471/progression-through-mitosis-promotes-parp-inhibitor-induced-cytotoxicity-in-homologous-recombination-deficient-cancer-cells
#17
Pepijn M Schoonen, Francien Talens, Colin Stok, Ewa Gogola, Anne Margriet Heijink, Peter Bouwman, Floris Foijer, Madalena Tarsounas, Sohvi Blatter, Jos Jonkers, Sven Rottenberg, Marcel A T M van Vugt
Mutations in homologous recombination (HR) genes BRCA1 and BRCA2 predispose to tumorigenesis. HR-deficient cancers are hypersensitive to Poly (ADP ribose)-polymerase (PARP) inhibitors, but can acquire resistance and relapse. Mechanistic understanding how PARP inhibition induces cytotoxicity in HR-deficient cancer cells is incomplete. Here we find PARP inhibition to compromise replication fork stability in HR-deficient cancer cells, leading to mitotic DNA damage and consequent chromatin bridges and lagging chromosomes in anaphase, frequently leading to cytokinesis failure, multinucleation and cell death...
July 17, 2017: Nature Communications
https://www.readbyqxmd.com/read/28712502/gene-editing-with-talen-and-crispr-cas-in-rice
#18
Honghao Bi, Bing Yang
Engineered, site-specific nucleases induce genomic double-strand DNA breaks and break repair processes enable genome editing in a plethora of eukaryotic genomes. TALENs (transcription activator-like effector nucleases) and CRISPR/Cas (clustered regularly interspaced short palindromic repeats and CRISPR-associated proteins) are potent biotechnological tools used for genome editing. In rice, species-tailored editing tools have proven to be efficient and easy to use. Both tools are capable of generating DNA double-strand breaks (DSBs) in vivo and such breaks can be repaired either by error-prone NHEJ (nonhomologous end joining) that leads to nucleotide insertions or deletions or by HDR (homology-directed repair) if an appropriate exogenous DNA template is provided...
2017: Progress in Molecular Biology and Translational Science
https://www.readbyqxmd.com/read/28712497/use-of-crispr-cas9-for-symbiotic-nitrogen-fixation-research-in-legumes
#19
Longlong Wang, Longxiang Wang, Yu Zhou, Deqiang Duanmu
Nitrogen-fixing rhizobia have established a symbiotic relationship with the legume family through more than 60 million years of evolution. Hundreds of legume host genes are involved in the SNF (symbiotic nitrogen fixation) process, such as recognition of the bacterial partners, nodulation signaling and nodule development, maintenance of highly efficient nitrogen fixation within nodules, regulation of nodule numbers, and nodule senescence. However, investigations of SNF-related gene functions and dissecting molecular mechanisms of the complicated signaling crosstalk on a genomic scale were significantly restricted by insufficient mutant resources of several representative model legumes...
2017: Progress in Molecular Biology and Translational Science
https://www.readbyqxmd.com/read/28710417/talen-based-hpv-e7-editing-triggers-necrotic-cell-death-in-cervical-cancer-cells
#20
Sumitra Shankar, Deepti Prasad, Rahul Sanawar, Ani V Das, M Radhakrishna Pillai
Human Papillomavirus E7 and E6 oncoproteins have been considered as suitable candidate anti-viral targets since they cause malignant conversion in cervical cancers. Transcription Activator-Like Effector Nucleases (TALENs) are recent editing tools to knockout genes by inducing double stranded breaks at specific sites in the genome. In here, we have designed specific TALENs to target E7 and analyzed their efficiency in inducing cell death in cervical cancer cells. We found that designed TALENs could yield about 10-12% editing activity as observed from T7E1 and nuclease resistance assays...
July 14, 2017: Scientific Reports
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