Pigs with δ-sarcoglycan deficiency exhibit traits of genetic cardiomyopathy

Matsunari, Hitomi; Honda, Michiyo; Watanabe, Masaru; Fukushima, Satsuki; Suzuki, Kota; Miyagawa, Shigeru; Nakano, K.; Umeyama, Kazuhiro; Uchikura, Ayuko; Okamoto, Ken‐ichi; Nagaya, Masaki; Toyo’oka, Toshimasa; Sawa, Yoshiki; Nagashima, Hiroshi

doi:10.1038/s41374-020-0406-7

Cited by 10 publications

(8 citation statements)

References 71 publications

(84 reference statements)

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“…[95][96][97][98] In this regard, engineered nuclease-mediated genome editing provides opportunities to modify the genomes of large animals, thereby making them applicable to modeling of diseases such as inherited cardiovascular diseases. 93,94,[98][99][100][101][102][103] Heterozygous pigs carrying the HCM point mutation R723G in the porcine MYH7 gene displayed HCM pathologies, including mild cardiomyocyte disarray, malformed nuclei, MYH7 overexpression, and neonatal lethality. 104 Schneider et al 105 generated RBM20 gene-edited pigs carrying a pathogenic R636Q mutation found in DCM patients.…”

Section: Modeling Inherited Heart Diseases In Large Animalsmentioning

confidence: 99%

CRISPR Modeling and Correction of Cardiovascular Disease

Liu

Olson

2022

Circulation Research

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Cardiovascular disease remains the leading cause of morbidity and mortality in the developed world. In recent decades, extraordinary effort has been devoted to defining the molecular and pathophysiological characteristics of the diseased heart and vasculature. Mouse models have been especially powerful in illuminating the complex signaling pathways, genetic and epigenetic regulatory circuits, and multicellular interactions that underlie cardiovascular disease. The advent of CRISPR genome editing has ushered in a new era of cardiovascular research and possibilities for genetic correction of disease. Next-generation sequencing technologies have greatly accelerated the identification of disease-causing mutations, and advances in gene editing have enabled the rapid modeling of these mutations in mice and patient-derived induced pluripotent stem cells. The ability to correct the genetic drivers of cardiovascular disease through delivery of gene editing components in vivo, while still facing challenges, represents an exciting therapeutic frontier. In this review, we provide an overview of cardiovascular disease mechanisms and the potential applications of CRISPR genome editing for disease modeling and correction. We also discuss the extent to which mice can faithfully model cardiovascular disease and the opportunities and challenges that lie ahead.

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Section: Modeling Inherited Heart Diseases In Large Animalsmentioning

confidence: 99%

CRISPR Modeling and Correction of Cardiovascular Disease

Liu

Olson

2022

Circulation Research

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“…(2018) [ 114 ] SGCD SCNT TALEN Matsunari et al . (2020) [ 128 ] Cryopyrin-associated periodic syndrome NLRP3 SCNT CRISPR Li et al . (2020) [ 116 ] Diabetes INS SCNT CRISPR Cho et al .…”

Section: Recent Trends In Gene Editing In Pigsmentioning

confidence: 99%

Current status of the application of gene editing in pigs

2021

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Genetically modified animals, especially rodents, are widely used in biomedical research. However, non-rodent models are required for efficient translational medicine and preclinical studies. Owing to the similarity in the physiological traits of pigs and humans, genetically modified pigs may be a valuable resource for biomedical research. Somatic cell nuclear transfer (SCNT) using genetically modified somatic cells has been the primary method for the generation of genetically modified pigs. However, site-specific gene modification in porcine cells is inefficient and requires laborious and time-consuming processes. Recent improvements in gene-editing systems, such as zinc finger nucleases, transcription activator-like effector nucleases, and the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein (CRISPR/Cas) system, represent major advances. The efficient introduction of site-specific modifications into cells via gene editors dramatically reduces the effort and time required to generate genetically modified pigs. Furthermore, gene editors enable direct gene modification during embryogenesis, bypassing the SCNT procedure. The application of gene editors has progressively expanded, and a range of strategies is now available for porcine gene engineering. This review provides an overview of approaches for the generation of genetically modified pigs using gene editors, and highlights the current trends, as well as the limitations, of gene editing in pigs.

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“…Other advantages of the pig model are its similarities in physiology, metabolism, genomics, and proteomics to humans [7][8][9][10]. Genetically modified pig disease models, such as the genetic cardiomyopathy model, have also been developed [11]. The current review updates the contributions of large animal models for research of cardiovascular medicine, especially focusing on the utility of pig models.…”

Section: Introductionmentioning

confidence: 99%

Large Animal Models in Cardiovascular Research

Osada¹,

Murata²,

Masumoto³

2023

Animal Models and Experimental Research in Medicine

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Studies of not only preclinical cardiovascular research but also those of life science, medical, and pharmacological fields commonly utilize small animal models. However, for the advancement of cardiovascular medicine, researches using large animal models are important step for preclinical validation of therapeutic efficacy and safety by virtue of having models with a body and heart size comparable with that of a human, providing clinically relevant experiments without the concern of over- or under-estimating therapeutic effects and risks. In particular, pigs are considered as a suitable animal model for research in cardiovascular medicine because of the similarities in physiology, metabolism, genomics, and proteomics to those in humans. Another advantage of pigs is the availability of various heart disease models such as myocardial infarction and genetically established cardiomyopathy. The present review updates the contributions of large animal model-based research to the development of cardiovascular medicine, especially focusing on the utility of pig models.

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Pigs with δ-sarcoglycan deficiency exhibit traits of genetic cardiomyopathy

Cited by 10 publications

References 71 publications

CRISPR Modeling and Correction of Cardiovascular Disease

CRISPR Modeling and Correction of Cardiovascular Disease

Current status of the application of gene editing in pigs

Large Animal Models in Cardiovascular Research

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