دورية أكاديمية
Genetic therapy in a mitochondrial disease model suggests a critical role for liver dysfunction in mortality
| العنوان: | Genetic therapy in a mitochondrial disease model suggests a critical role for liver dysfunction in mortality |
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| المؤلفون: | Sabharwal, Ankit, Wishman, Mark D, Cervera, Roberto Lopez, Serres, MaKayla R, Anderson, Jennifer L, Holmberg, Shannon R, Kar, Bibekananda, Treichel, Anthony J, Ichino, Noriko, Liu, Weibin, Yang, Jingchun, Ding, Yonghe, Deng, Yun, Lacey, Jean M, Laxen, William J, Loken, Perry R, Oglesbee, Devin, Farber, Steven A, Clark, Karl J, Xu, Xiaolei, Ekker, Stephen C |
| المساهمون: | National Institutes of Health, Marriott Foundation, Mayo Foundation for Medical Education and Research, Carnegie Institution for Science, G. Harold and Leila Y. Mathers Charitable Foundation |
| المصدر: | eLife ; volume 11 ; ISSN 2050-084X |
| بيانات النشر: | eLife Sciences Publications, Ltd |
| سنة النشر: | 2022 |
| المجموعة: | eLife (E-Journal - via CrossRef) |
| الوصف: | The clinical and largely unpredictable heterogeneity of phenotypes in patients with mitochondrial disorders demonstrates the ongoing challenges in the understanding of this semi-autonomous organelle in biology and disease. Previously, we used the gene-breaking transposon to create 1200 transgenic zebrafish strains tagging protein-coding genes (Ichino et al., 2020), including the lrpprc locus. Here, we present and characterize a new genetic revertible animal model that recapitulates components of Leigh Syndrome French Canadian Type (LSFC), a mitochondrial disorder that includes diagnostic liver dysfunction. LSFC is caused by allelic variations in the LRPPRC gene, involved in mitochondrial mRNA polyadenylation and translation. lrpprc zebrafish homozygous mutants displayed biochemical and mitochondrial phenotypes similar to clinical manifestations observed in patients, including dysfunction in lipid homeostasis. We were able to rescue these phenotypes in the disease model using a liver-specific genetic model therapy, functionally demonstrating a previously under-recognized critical role for the liver in the pathophysiology of this disease. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.7554/elife.65488 |
| الإتاحة: | https://doi.org/10.7554/elife.65488Test https://cdn.elifesciences.org/articles/65488/elife-65488-v3.pdfTest https://cdn.elifesciences.org/articles/65488/elife-65488-v3.xmlTest https://elifesciences.org/articles/65488Test |
| حقوق: | http://creativecommons.org/licenses/by/4.0Test/ ; http://creativecommons.org/licenses/by/4.0Test/ ; http://creativecommons.org/licenses/by/4.0Test/ |
| رقم الانضمام: | edsbas.B93BA6DA |
| قاعدة البيانات: | BASE |
| DOI: | 10.7554/elife.65488 |
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