Impact of Essential Genes on the Success of Genome Editing Experiments Generating 3,313 New Genetically Engineered Mouse Lines
説明
<jats:title>Abstract</jats:title><jats:p>The International Mouse Phenotyping Consortium (IMPC) systematically produces and phenotypes mouse lines with presumptive null mutations to provide insight into gene function. The IMPC now uses the programmable RNA-guided nuclease Cas9 for its increased capacity and flexibility to efficiently generate null alleles in the C57BL/6N strain. In addition to being a valuable novel and accessible research resource, the production of 3,313 knockout mouse lines using comparable protocols provides a rich dataset to analyze experimental and biological variables affecting<jats:italic>in vivo</jats:italic>gene engineering with Cas9. Mouse line production has two critical steps – generation of founders with the desired allele and germline transmission (GLT) of that allele from founders to offspring. A systematic evaluation of the variables impacting success rates identified gene essentiality as the primary factor influencing successful production of null alleles. Collectively, our findings provide best practice recommendations for using Cas9 to generate alleles in mouse essential genes, many of which are orthologs of genes linked to human disease.</jats:p>
収録刊行物
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- Scientific Reports
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Scientific Reports 14 2021-10-06
Cold Spring Harbor Laboratory
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キーワード
- Male
- Mouse
- 1.1 Normal biological development and functioning
- Knockout
- Science
- Inbred C57BL
- Article
- Mice
- Essential
- Genetics
- Animals
- Cas9
- Alleles
- Gene Editing
- Mice, Knockout
- Genes, Essential
- Q
- R
- Biological Sciences
- Mice, Inbred C57BL
- Phenotype
- Genes
- Medicine
- Female
- International Mouse Phenotyping Consortium
- CRISPR-Cas Systems
- Genetic Engineering
- Biotechnology
- Genome editing
詳細情報 詳細情報について
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- CRID
- 1872553967379565184
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- ISSN
- 20452322
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- データソース種別
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- OpenAIRE