Application of an F0-based genetic assay in adult zebrafish to identify modifier genes of an inherited cardiomyopathy
| العنوان: | Application of an F0-based genetic assay in adult zebrafish to identify modifier genes of an inherited cardiomyopathy |
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| المؤلفون: | Yonghe Ding, Mingmin Wang, Haisong Bu, Jiarong Li, Xueying Lin, Xiaolei Xu |
| المصدر: | Disease Models & Mechanisms. 16 |
| بيانات النشر: | The Company of Biologists, 2022. |
| سنة النشر: | 2022 |
| مصطلحات موضوعية: | Gene Knockout Techniques, Genes, Modifier, Immunology and Microbiology (miscellaneous), Neuroscience (miscellaneous), Animals, Medicine (miscellaneous), Zebrafish Proteins, Apoptosis Regulatory Proteins, Cardiomyopathies, Zebrafish, General Biochemistry, Genetics and Molecular Biology, Adaptor Proteins, Signal Transducing, RNA, Guide, Kinetoplastida |
| الوصف: | Modifier genes contribute significantly to our understanding of pathophysiology in human diseases; however, effective approaches to identify modifier genes are still lacking. Here, we aim to develop a rapid F0-based genetic assay in adult zebrafish using the bag3 gene knockout (bag3e2/e2) cardiomyopathy model as a paradigm. First, by utilizing a classic genetic breeding approach, we identified dnajb6b as a deleterious modifier gene for bag3 cardiomyopathy. Next, we established an F0-based genetic assay in adult zebrafish through injection of predicted microhomology-mediated end joining (MMEJ)-inducing single guide RNA/Cas9 protein complex. We showed that effective gene knockdown is maintained in F0 adult fish, enabling recapitulation of both salutary modifying effects of the mtor haploinsufficiency and deleterious modifying effects of the dnajb6b gene on bag3 cardiomyopathy. We finally deployed the F0-based genetic assay to screen differentially expressed genes in the bag3 cardiomyopathy model. As a result, myh9b was identified as a novel modifier gene for bag3 cardiomyopathy. Together, these data prove the feasibility of an F0 adult zebrafish-based genetic assay that can be effectively used to discover modifier genes for inherited cardiomyopathy. |
| تدمد: | 1754-8411 1754-8403 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d9fd5cb71c933c5168ab797c0987e8ef https://doi.org/10.1242/dmm.049427 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....d9fd5cb71c933c5168ab797c0987e8ef |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 17548411 17548403 |
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