Autor: |
Seonghyun Lee, Hyunji Lee, Gayoung Baek, Eunji Namgung, Joo Min Park, Sanghun Kim, Seongho Hong, Jin-Soo Kim |
Jazyk: |
angličtina |
Rok vydání: |
2022 |
Předmět: |
|
Zdroj: |
Genome Biology, Vol 23, Iss 1, Pp 1-10 (2022) |
Druh dokumentu: |
article |
ISSN: |
1474-760X |
DOI: |
10.1186/s13059-022-02782-z |
Popis: |
Abstract We present two methods for enhancing the efficiency of mitochondrial DNA (mtDNA) editing in mice with DddA-derived cytosine base editors (DdCBEs). First, we fused DdCBEs to a nuclear export signal (DdCBE-NES) to avoid off-target C-to-T conversions in the nuclear genome and improve editing efficiency in mtDNA. Second, mtDNA-targeted TALENs (mitoTALENs) are co-injected into mouse embryos to cleave unedited mtDNA. We generated a mouse model with the m.G12918A mutation in the MT-ND5 gene, associated with mitochondrial genetic disorders in humans. The mutant mice show hunched appearances, damaged mitochondria in kidney and brown adipose tissues, and hippocampal atrophy, resulting in premature death. |
Databáze: |
Directory of Open Access Journals |
Externí odkaz: |
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