Genetic Engineering of Zebrafish in Cancer Research

Raby, Ludivine; Völkel, Pamela; Bourhis, Xuefen Le; Angrand, Pierre‐Olivier

doi:10.3390/cancers12082168

Cited by 34 publications

(15 citation statements)

References 258 publications

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“…Genome engineering technologies have been heavily utilized in zebrafish disease modelling. A recent review catalogued and thoroughly discussed available technologies, and we encourage readers to consult this review for information on forward genetic screens using chemical mutagens, TILLING (Targeting Induced Local Lesions IN Genomes), transgenic techniques, gene editing using Zinc Finger Nucleases (ZFN), TAL-effector Endonucleases (TALEN) and Clustered Regularly Interspaced Palindromic Repeats (CRISPR)/Cas9 strategies ( Raby et al, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

Zebrafish Cancer Predisposition Models

Kobar

Collett

Prykhozhij

et al. 2021

Front. Cell Dev. Biol.

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Cancer predisposition syndromes are rare, typically monogenic disorders that result from germline mutations that increase the likelihood of developing cancer. Although these disorders are individually rare, resulting cancers collectively represent 5–10% of all malignancies. In addition to a greater incidence of cancer, affected individuals have an earlier tumor onset and are frequently subjected to long-term multi-modal cancer screening protocols for earlier detection and initiation of treatment. In vivo models are needed to better understand tumor-driving mechanisms, tailor patient screening approaches and develop targeted therapies to improve patient care and disease prognosis. The zebrafish (Danio rerio) has emerged as a robust model for cancer research due to its high fecundity, time- and cost-efficient genetic manipulation and real-time high-resolution imaging. Tumors developing in zebrafish cancer models are histologically and molecularly similar to their human counterparts, confirming the validity of these models. The zebrafish platform supports both large-scale random mutagenesis screens to identify potential candidate/modifier genes and recently optimized genome editing strategies. These techniques have greatly increased our ability to investigate the impact of certain mutations and how these lesions impact tumorigenesis and disease phenotype. These unique characteristics position the zebrafish as a powerful in vivo tool to model cancer predisposition syndromes and as such, several have already been created, including those recapitulating Li-Fraumeni syndrome, familial adenomatous polyposis, RASopathies, inherited bone marrow failure syndromes, and several other pathogenic mutations in cancer predisposition genes. In addition, the zebrafish platform supports medium- to high-throughput preclinical drug screening to identify compounds that may represent novel treatment paradigms or even prevent cancer evolution. This review will highlight and synthesize the findings from zebrafish cancer predisposition models created to date. We will discuss emerging trends in how these zebrafish cancer models can improve our understanding of the genetic mechanisms driving cancer predisposition and their potential to discover therapeutic and/or preventative compounds that change the natural history of disease for these vulnerable children, youth and adults.

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Section: Introductionmentioning

confidence: 99%

Zebrafish Cancer Predisposition Models

Kobar

Collett

Prykhozhij

et al. 2021

Front. Cell Dev. Biol.

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“…For instance, zebrafish has emerged as an important model organism for human cancer and models of hematological malignancies including myeloproliferative neoplasm (MPN), acute myeloid leukemia (AML), chronic myeloid leukemia (CML) and acute lymphoblastic leukemia (ALL) with highly conserved oncogenic pathways and pharmacologic responses were reported. [59][60][61][62][63] With the well-developed methodologies in autophagy study 32,39,64 and genetic engineering, 65 zebrafish could be developed into a unique modelling platform to define the role of autophagy in hematological malignancies, which will provide important information for the development of autophagy-related therapeutic strategies against these heterogeneous diseases.…”

Section: Discussionmentioning

confidence: 99%

Genetic and chemical inhibition of autophagy in zebrafish induced myeloproliferation

Hasan

Chen

Zhang

et al. 2021

Preprint

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Autophagy is an evolutionary conserved and dynamic lysosomal degradation process for cellular homeostasis and remodelling, which is essential for the development and maintenance of different hematopoietic fates. However, the roles of autophagy in definitive hematopoiesis remain elusive. Here, we exploited zebrafish (Danio rerio) to investigate the effect of knocking-out unc-51 like autophagy activating kinase 1b and 2 (ulk1b and ulk2), homologous of human ULK1 and ULK2, respectively, on definitive hematopoiesis. Upon ulk1b or ulk2 mutation, autophagosome formation was blocked in zebrafish embryos. More importantly, pan-leukocytes (lcp1), common myeloid progenitors (spi1b), neutrophils (mpx), and macrophages (mpeg1.1) significantly elevated, while the hematopoietic stem and progenitor cell (HSPC) (myb), erythroid progenitors (gata1), and embryonic hemoglobin (hbae1.1) significantly reduced in the caudal hematopoietic tissue (CHT) of ulk1b or ulk2 mutant zebrafish embryos. On the other hand, chemically modulated autophagy induction by calpeptin, a downstream autophagy inducer for ulk complex, was insufficient to ameliorate dysregulated hematopoiesis in both ulk1b and ulk2 mutants. Conversely, autophagy inhibitor 3-Methyladenine functioned parallelly with the ulk mutants to maintain defective hematopoiesis. These observations raised a link between autophagy and definitive hematopoiesis and potentiates the fact that autophagy deficiency incorporates with myeloproliferation and anemia, which warrants the significance of autophagy in regulating definitive hematopoiesis.

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“…However, the procedure of TILLING is costly, labor intensive, and cannot be implemented in most individual labs. The most important thing is that the identification of mutant genes is very troublesome, and whether there are multiple mutation sites cannot be well determined [ 21 ].…”

Section: Targeting Induced Local Lesions In Genomes (Tilling)mentioning

confidence: 99%

Progress in Gene-Editing Technology of Zebrafish

Jia

Zhang

et al. 2021

Biomolecules

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As a vertebrate model, zebrafish (Danio rerio) plays a vital role in the field of life sciences. Recently, gene-editing technology has become increasingly innovative, significantly promoting scientific research on zebrafish. However, the implementation of these methods in a reasonable and accurate manner to achieve efficient gene-editing remains challenging. In this review, we systematically summarize the development and latest progress in zebrafish gene-editing technology. Specifically, we outline trends in double-strand break-free genome modification and the prospective applications of fixed-point orientation transformation of any base at any location through a multi-method approach.

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Genetic Engineering of Zebrafish in Cancer Research

Cited by 34 publications

References 258 publications

Zebrafish Cancer Predisposition Models

Zebrafish Cancer Predisposition Models

Genetic and chemical inhibition of autophagy in zebrafish induced myeloproliferation

Progress in Gene-Editing Technology of Zebrafish

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