The production of 4,182 mouse lines identifies experimental and biological variables impacting Cas9-mediated mutant mouse line production
Elrick, H.; Peterson, K. A.; Wood, J. A.; Lanza, D. G.; Acar, E. F.; Teboul, L.; Ryder, E. J.; Ayabe, S.; Birling, M.-C.; Caulder, A.; Chiani, F.; Codner, G. F.; Doe, B.; Duddy, G.; Gambadoro, A.; Gertsenstein, M.; Gomez-Segura, A.; Goodwin, L. O.; Ju, C.; Kasparek, P.; King, R. E.; Lee, D.; Lee, H.; Lintott, L. G.; Liu, Z.; Lorenzo, I.; Mackenzie, M.; Marschall, S.; Matthews, P.; Ruhe, M.; Santos, L.; Seavitt, J. R.; Seisenberger, C.; Wardle-Jones, H.; Willis, B. J.; Zhang, J.; Zhao, J.; Zhou, F.; Adams, D. J.; Bradley, A.; Braun, R. E.; DeMayo, F. J.; Dickinson, M. E.; Gao, X.; Herault, Y.;
Show abstract
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 in vivo 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.
Matching journals
The top 5 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- CRISPR-Cas9 cytidine and adenosine base editing of splice-sites mediates highly-efficient disruption of proteins in primary cells 96%
- Improved prime editors enable pathogenic allele correction and cancer modelling in adult mice 96%
- Single generation allele introgression into pure chicken breeds using Sire Dam Surrogate (SDS) mating 95%
Similar papers in this journal
- Translating GWAS-identified loci for cardiac rhythm and rate using an in vivo image- and CRISPR/Cas9/based approach 95%
- A selectable, plasmid-based system to generate CRISPR/Cas9 gene edited and knock-in mosquito cell lines 94%
- A Vector System Encoding Histone H3 Mutants Facilitates Manipulations of the Neuronal Epigenome 94%
Similar papers in this journal
Similar papers in this journal
- CRISPR/Cas9 targeting Ttc30a mimics ciliary chondrodysplasia with polycystic kidney disease. 94%
- Dynamic regulation and requirement for ribosomal RNA transcription duringmammalian development 94%
- Specialization of the photoreceptor transcriptome by Srrm3-dependent microexons is required for outer segment maintenance and vision 93%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.