RSPO2 inhibition of RNF43 and ZNRF3 governs limb development independently of LGR4/5/6

Nature, Journal Year: 2018, Volume and Issue: 557(7706), P. 564 - 569

Published: May 1, 2018

Language: Английский

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Expanding the genetic toolkit in Xenopus: Approaches and opportunities for human disease modeling

Developmental Biology, Journal Year: 2016, Volume and Issue: 426(2), P. 325 - 335

Published: April 29, 2016

The amphibian model Xenopus, has been used extensively over the past century to study multiple aspects of cell and developmental biology. Xenopus offers advantages a non-mammalian system, including high fecundity, external development, simple housing requirements, with additional large embryos, highly conserved processes, close evolutionary relationship higher vertebrates. There are two main species in biomedical research, laevis tropicalis; common perception is that both excellent models for embryological biological studies, but only tropicalis useful as genetic model. recent completion genome sequence combined implementation editing tools, such TALENs (transcription activator-like effector nucleases) CRISPR-Cas (clustered regularly interspaced short palindromic repeats-CRISPR associated nucleases), greatly facilitates use understanding gene function development disease. In this paper, we review advances made discuss various approaches have generate knockout knock-in animals species. These show particular counters notion not amenable manipulations.

Language: Английский

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The genetic basis of colonic adenomatous polyposis syndromes

Hereditary Cancer in Clinical Practice, Journal Year: 2017, Volume and Issue: 15(1)

Published: March 16, 2017

Colorectal cancer (CRC) is one of the most common forms worldwide and familial adenomatous polyposis (FAP) accounts for approximately 1% all CRCs. Adenomatous syndromes can be divided into; – classic FAP attenuated (AFAP), MUTYH-associated (MAP), NTHL1-associated (NAP) polymerase proofreading-associated (PPAP). The genetics clinical manifestation disease varies cases with diagnosis might molecularly show a different diagnosis. This review examines aspects disease; in addition genotype-phenotype modifier alleles will discussed. New technology has made it possible to diagnose some APC mutation negative patients into their respective syndromes. There still remain many undiagnosed indicating that there causative genes discovered today's these are expected identified near future. knowledge about role contribute improved pre-symptomatic treatment. novel mutations continually already associated new polyposis. search should priority.

Language: Английский

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Xenbase: Facilitating the Use of Xenopus to Model Human Disease

Frontiers in Physiology, Journal Year: 2019, Volume and Issue: 10

Published: Feb. 26, 2019

At a fundamental level most genes, signaling pathways, biological functions and organ systems are highly conserved between man all vertebrate species. Leveraging this conservation, researchers increasingly using the experimental advantages of amphibian Xenopus to model human disease. The online resource, Xenbase, enables disease modeling by curating literature published in PubMed integrating these data with orthologous anatomy, more recently links Online Mendelian Inheritance Man resource (OMIM) Human Disease Ontology (DO). Here we review how Xenbase supports report on meta-analysis research providing an overview different types diseases being modeled variety approaches used. Text mining over 50,000 articles imported into from identified approximately 1,000 putative disease- articles. These were manually assessed annotated ontologies, which then used classify papers based type. We found that is study diverse array three main approaches: cell-free egg extracts aspects cellular molecular biology, oocytes ion transport channel physiology embryo experiments focused congenital diseases. integrated Pages allow easy navigation information external databases. Results analysis will equip suite available or dissect pathological process. Ideally clinicians basic use foster collaborations necessary interrogate development treatment

Language: Английский

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CRISPR/Cas9 mediated knockout of rb1 and rbl1 leads to rapid and penetrant retinoblastoma development in Xenopus tropicalis

Scientific Reports, Journal Year: 2016, Volume and Issue: 6(1)

Published: Oct. 14, 2016

Abstract Retinoblastoma is a pediatric eye tumor in which bi-allelic inactivation of the 1 ( RB1 ) gene initiating genetic lesion. Although recently curative rates retinoblastoma have increased, there are at this time no molecular targeted therapies available. This is, part, due to lack highly penetrant and rapid animal models that facilitate identification targets allow therapeutic intervention. Different mouse available, all based on deactivation both Rb1 Retinoblastoma-like Rbl1 ), each showing different kinetics development. Here, we show by CRISPR/Cas9 techniques similar mouse, neither rb1 nor rbl1 single mosaic mutant Xenopus tropicalis develop tumors, whereas / double tadpoles rapidly retinoblastoma. Moreover, occasionally presence pinealoblastoma (trilateral retinoblastoma) was detected. We thus present first mediated cancer model genuine non-mammalian model. The our paves way for use as pre-clinical Additionally, provides unique possibilities fast elucidation novel drug triple multiplex gRNA injections + modifier order address clinically unmet need therapy.

Language: Английский

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Applications of Genome Editing Technology in Animal Disease Modeling and Gene Therapy

Computational and Structural Biotechnology Journal, Journal Year: 2019, Volume and Issue: 17, P. 689 - 698

Published: Jan. 1, 2019

Genome editing technology is a technique for targeted genetic modifications, enabling the knockout and addition of specific DNA fragments. This has been widely used in various types biomedical research, clinics agriculture. In terms disease constructing appropriate animal models necessary. Combining reproductive with genome editing, many have generated basic clinical research. addition, precisely modifications allow to flourish field gene therapy. Many mutations refractory traditional therapy could be permanently corrected at level. Thus, undoubtedly promising this review, we mainly introduce applications therapies, as well its future prospects challenges.

Language: Английский

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Advances in the Xenopus immunome: Diversification, expansion, and contraction

Developmental & Comparative Immunology, Journal Year: 2023, Volume and Issue: 145, P. 104734 - 104734

Published: May 10, 2023

Language: Английский

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Using Xenopus to understand human disease and developmental disorders

genesis, Journal Year: 2017, Volume and Issue: 55(1-2)

Published: Jan. 1, 2017

Model animals are crucial to biomedical research. Among the commonly used model animals, amphibian, Xenopus, has had tremendous impact because of its unique experimental advantages, cost effectiveness, and close evolutionary relationship with mammals as a tetrapod. Over past 50 years, use Xenopus made possible many fundamental contributions biomedicine, it is cornerstone research in cell biology, developmental immunology, molecular neurobiology, physiology. The prospects for an system excellent: uniquely well-suited contemporary approaches study biological disease mechanisms. Moreover, recent advances high throughput DNA sequencing, genome editing, proteomics, pharmacological screening easily applicable enabling rapid functional genomics human modeling at systems level.

Language: Английский

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TALENs and CRISPR/Cas9 fuel genetically engineered clinically relevant Xenopus tropicalis tumor models

genesis, Journal Year: 2017, Volume and Issue: 55(1-2)

Published: Jan. 1, 2017

Abstract The targeted nuclease revolution (TALENs, CRISPR/Cas9) now allows Xenopus researchers to rapidly generate custom on‐demand genetic knockout models. These novel methods perform reverse genetics are unprecedented and fueling a wide array of human disease models within the aquatic diploid model organism tropicalis (X. tropicalis) . This emerging technology review focuses on tools genetically engineered X. (GEXM), with focus establishment genuine clinically relevant cancer We believe that due particular advantageous characteristics, outlined this review, GEXM will become valuable alternative animal for modeling cancer. Furthermore, we provide perspectives how be used as platform elucidation therapeutic targets preclinical drug validation. Finally, also discuss some future prospects recent expansions adaptations CRISPR/Cas9 toolbox might influence push forward research.

Language: Английский

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BLM promotes the activation of Fanconi Anemia signaling pathway

Oncotarget, Journal Year: 2016, Volume and Issue: 7(22), P. 32351 - 32361

Published: April 12, 2016

// Jayabal Panneerselvam 1 , Hong Wang 2, 3 Jun Zhang 2 Raymond Che Herbert Yu Peiwen Fei University of Hawaii Cancer Center, Hawaii, Honolulu, HI, USA Department Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, Current address: Sun Yat-Sen University, Guangzhou, China Correspondence to: Fei, email: [email protected] Keywords: Fanconi Anemia, BLM, FANCD2 monoubiquitination, DNA damage, tumorigenesis Received: October 25, 2015 Accepted: March 28, 2016 Published: April 12, ABSTRACT Mutations in the human RecQ helicase, causes Bloom Syndrome, which is a rare autosomal recessive disorder characterized by genomic instability an increased risk cancer. Anemia (FA), resulting from mutations any 19 known FA genes those yet to be known, also chromosomal high incidence BLM helicase proteins, therefore, may work common tumor-suppressor signaling pathway. To date, it remains largely unclear as how proteins concurrently maintenance genome stability. Here we report that involved early activation group D2 protein (FANCD2). We found substantially delayed attenuated crosslinking agent-treated cells harboring deficient Blm compared similarly treated control with sufficient BLM. identified domain VI plays essential role promoting agents, especially ultraviolet B. The similar biological effects performed ΔVI-BLM inactivated further confirm relationship between FANCD2. within detected cancer samples demonstrate functional importance this domain, suggesting tumorigenicity mtBLM at least partly attributed mitigated activation. Collectively, our data show previously unknown regulatory liaison advancing understanding susceptibility gene products act concert maintain

Language: Английский

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