Generation and Application of the Zebrafish heg1 Mutant as a Cardiovascular Disease Model

Lu, Shuxian; Hu, Mengyan; Wang, Wenwen; Liu, Hongkai; Kou, Yao; Lyu, Zhaojie; Tian, Jing

doi:10.3390/biom10111542

Cited by 28 publications

(21 citation statements)

References 52 publications

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“…The heg1 CRISPR zebrafish mutant developed severe cardiovascular malformations, including an abnormal heart rate, atrial ventricular enlargement, venous thrombosis, and slow blood flow. All these symptoms are similar to those associated with human heart failure and thrombosis ( Lu SX et al, 2020 ). Thus, the zebrafish heg1 CRISPR mutant has potential to serve as an animal model for analyzing the pathogenesis of cardiovascular diseases, and screening and testing new drugs and their potential therapeutic targets.…”

Section: Wide Use Of Crispr/cas In Clinical and Preclinical Researcsupporting

confidence: 62%

“…Cardiovascular disease is the leading cause of global death and threatens millions of people in their daily lives. Recently, Lu SX et al (2020) knocked out heg1 , a gene encoding a heart development protein with epidermal growth factor (EGF) like domains 1, in zebrafish. The heg1 CRISPR zebrafish mutant developed severe cardiovascular malformations, including an abnormal heart rate, atrial ventricular enlargement, venous thrombosis, and slow blood flow.…”

Section: Wide Use Of Crispr/cas In Clinical and Preclinical Researcmentioning

confidence: 99%

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CRISPR/Cas: a Nobel Prize award-winning precise genome editing technology for gene therapy and crop improvement

Brant

Budak

et al. 2021

J. Zhejiang Univ. Sci. B

123

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Since it was first recognized in bacteria and archaea as a mechanism for innate viral immunity in the early 2010s, clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein (Cas) has rapidly been developed into a robust, multifunctional genome editing tool with many uses. Following the discovery of the initial CRISPR/Cas-based system, the technology has been advanced to facilitate a multitude of different functions. These include development as a base editor, prime editor, epigenetic editor, and CRISPR interference (CRISPRi) and CRISPR activator (CRISPRa) gene regulators. It can also be used for chromatin and RNA targeting and imaging. Its applications have proved revolutionary across numerous biological fields, especially in biomedical and agricultural improvement. As a diagnostic tool, CRISPR has been developed to aid the detection and screening of both human and plant diseases, and has even been applied during the current coronavirus disease 2019 (COVID-19) pandemic. CRISPR/Cas is also being trialed as a new form of gene therapy for treating various human diseases, including cancers, and has aided drug development. In terms of agricultural breeding, precise targeting of biological pathways via CRISPR/Cas has been key to regulating molecular biosynthesis and allowing modification of proteins, starch, oil, and other functional components for crop improvement. Adding to this, CRISPR/Cas has been shown capable of significantly enhancing both plant tolerance to environmental stresses and overall crop yield via the targeting of various agronomically important gene regulators. Looking to the future, increasing the efficiency and precision of CRISPR/Cas delivery systems and limiting off-target activity are two major challenges for wider application of the technology. This review provides an in-depth overview of current CRISPR development, including the advantages and disadvantages of the technology, recent applications, and future considerations.

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Section: Wide Use Of Crispr/cas In Clinical and Preclinical Researcsupporting

confidence: 62%

Section: Wide Use Of Crispr/cas In Clinical and Preclinical Researcmentioning

confidence: 99%

CRISPR/Cas: a Nobel Prize award-winning precise genome editing technology for gene therapy and crop improvement

Brant

Budak

et al. 2021

J. Zhejiang Univ. Sci. B

123

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“…Embryonic zebrafish heg1 mutants show signs of severe HF ( Mably et al, 2003 ). heg1 knockout zebrafish generated with CRISPR-Cas9 show atrial and ventricular enlargement, slow heart rate and blood flow, and pericardial edema ( Lu et al, 2020 ). The authors used this DCM model for drug screening.…”

Section: Genetic Heart Failure Modelsmentioning

confidence: 99%

Zebrafish Heart Failure Models

Narumanchi

Wang

Perttunen

et al. 2021

Front. Cell Dev. Biol.

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Heart failure causes significant morbidity and mortality worldwide. The understanding of heart failure pathomechanisms and options for treatment remain incomplete. Zebrafish has proven useful for modeling human heart diseases due to similarity of zebrafish and mammalian hearts, fast easily tractable development, and readily available genetic methods. Embryonic cardiac development is rapid and cardiac function is easy to observe and quantify. Reverse genetics, by using morpholinos and CRISPR-Cas9 to modulate gene function, make zebrafish a primary animal model for in vivo studies of candidate genes. Zebrafish are able to effectively regenerate their hearts following injury. However, less attention has been given to using zebrafish models to increase understanding of heart failure and cardiac remodeling, including cardiac hypertrophy and hyperplasia. Here we discuss using zebrafish to study heart failure and cardiac remodeling, and review zebrafish genetic, drug-induced and other heart failure models, discussing the advantages and weaknesses of using zebrafish to model human heart disease. Using zebrafish models will lead to insights on the pathomechanisms of heart failure, with the aim to ultimately provide novel therapies for the prevention and treatment of heart failure.

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“…Counting was performed using a mechanical counter and stopwatch. The heart rate was expressed as beats per minute (bpm) [ 23 , 24 ].…”

Section: Methodsmentioning

confidence: 99%

Phytochemical and Safety Evaluations of Zingiber ottensii Valeton Essential Oil in Zebrafish Embryos and Rats

Thitinarongwate

Mektrirat

Nimlamool

et al. 2021

Toxics

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Zingiber ottensii Valeton (ZO) exhibits pharmacological activity and has long been used in traditional medicine. However, reports about its safety profiles are limited. The present study aimed to evaluate the phytochemical profile and the toxic effects of ZO essential oil on the development of zebrafish and acute oral toxicity in rats. The essential oil was isolated from ZO rhizomes, and phytochemicals were analyzed using a gas chromatography–mass spectrometer (GC–MS). The embryotoxic and teratogenic effects of ZO essential oil were evaluated in zebrafish embryos and larvae and the acute oral toxicity was determined in rats. GC–MS results showed the essential oil contained zerumbone as a major phytoconstituent (24.73%). The zebrafish embryotoxicity of ZO essential oil appeared to be concentration- and time-dependent manner, with a moderate LC50 (1.003 µg/mL). Teratogenicity in zebrafish embryos also included morphological defects, decreased hatchability, and reduced heart rate. In rats, ZO essential oil (2000 mg/kg, p.o.) resulted in no mortality or significant toxicities. These findings suggest that ZO has embryotoxic and teratogenic effects in zebrafish embryos but does not result in death or acute oral toxicity in rats. Further long-term toxicity studies are needed to confirm the safety of products developed from ZO essential oil.

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Generation and Application of the Zebrafish heg1 Mutant as a Cardiovascular Disease Model

Cited by 28 publications

References 52 publications

CRISPR/Cas: a Nobel Prize award-winning precise genome editing technology for gene therapy and crop improvement

CRISPR/Cas: a Nobel Prize award-winning precise genome editing technology for gene therapy and crop improvement

Zebrafish Heart Failure Models

Phytochemical and Safety Evaluations of Zingiber ottensii Valeton Essential Oil in Zebrafish Embryos and Rats

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