| Title: |
Impact of essential genes on the success of genome editing experiments generating 3313 new genetically engineered mouse lines |
| Authors: |
Elrick, Hillary; Peterson, Kevin, A; Willis, Brandon, J; Lanza, Denise, G; Acar, Elif, F; Ryder, Edward, J; Teboul, Lydia; Kasparek, Petr; Birling, Marie-Christine; Adams, David, J; Bradley, Allan; Braun, Robert, E; Brown, Steve, D; Caulder, Adam; Codner, Gemma, F; Demayo, Francesco, J; Dickinson, Mary, E; Doe, Brendan; Duddy, Graham; Gertsenstein, Marina; Goodwin, Leslie, O; Hérault, Yann; Lintott, Lauri, G; Lloyd, K, C Kent; Lorenzo, Isabel; Mackenzie, Matthew; Mallon, Ann-Marie; Mckerlie, Colin; Parkinson, Helen; Ramirez-Solis, Ramiro; Seavitt, John, R; Sedlacek, Radislav; Skarnes, William, C; Smedley, Damien; Wells, Sara; White, Jacqueline, K; Wood, Joshua, A; Akhtar, Shaheen; Allan, Alasdair, J; Allen, Susan; André, Philippe; Archer, Daniel; Atkins, Sarah; Avery, Ruth; Ayadi, Abdel; Barrett, Daniel; Beyetinova, Tanya; Bell, Toni; Berry, Melissa; Boroviak, Katharina; Bottomley, Joanna; Brendler-Spaeth, Tim; Brown, Ellen; Burvill, Jonathan; Bussell, James; Cardeno, Charis; Carter, Rebecca, V; Castellanos-Penton, Patricia; Christou, Skevoulla; Clark, Greg; Clarke, Shannon; Cleak, James; Crawford, Ronnie; Creighton, Amie; Cruz, Maribelle; Danisment, Ozge; Davis, Charlotte; Doran, Joanne; Erbs, Valérie; Fan-Lan, Qing; Fell, Rachel; Feng, He; Fougerolle, Jean-Victor; Fower, Alex; Frake, Gemma; Fray, Martin, D; Galli, Antonella; Gannon, David; Gardiner, Wendy, J; Gaspero, Angelina; Gleeson, Diane; Godbehere, Chris; Grau, Evelyn; Griffiths, Mark; Griggs, Nicola; Grimsrud, Kristin; Hazeltine, Sarah; Hutchison, Marie; Ingle, Catherine; Iyer, Vivek; Jager, Kayla; Joeng, Joanna; Kales, Susan; Kaur, Perminder; Kenyon, Janet; Kopkanova, Jana; Kujath, Christelle; Kundi, Helen; Kutny, Peter; Laurin, Valerie; Lejeay, Sandrine; Lelliott, Christopher; Loeffler, Jorik; Lorentz, Romain; Mccabe, Christopher, V; Malzer, Elke; Matthews, Peter; Maswood, Ryea; Mckay, Matthew; Meehan, Terrence; Melvin, David; Murphy, Alison; Nakhuda, Asif; Patel, Amit; Paulavets, Ilya; Pavlovic, Guillaume; Pawelka, Ashley; Pike, Fran, J; Platte, Radka; Price, Peter, D; Rajaya, Kiran; Reddy, Shalini; Rich, Whitney; Rosen, Barry; Ross, Victoria; Ruhe, Mark; Santos, Luis; Schaeffer, Laurence; Schwiening, Alix; Selloum, Mohammed; Sethi, Debarati; Sidiangco, Jan, R; Sinclair, Caroline; Sins, Elodie; Sleep, Gillian; Sorg, Tania; Starbuck, Becky; Stewart, Michelle; Swash, Holly; Thomas, Mark; Tondat, Sandra; Urban, Rachel; Urbanova, Jana; Varley, Susan; von Schiller, Dominque; Wardle-Jones, Hannah; Weavers, Lauren; Woods, Michael; Murray, Stephen, A; Heaney, Jason, D; Nutter, Lauryl, M J |
| Contributors: |
Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC); Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS); ANR-10-IDEX-0002,UNISTRA,Par-delà les frontières, l'Université de Strasbourg(2010); ANR-10-LABX-0030,INRT,Integrative Biology : Nuclear dynamics- Regenerative medicine - Translational medicine(2010); ANR-10-INBS-0007,PHENOMIN,INFRASTRUCTURE NATIONALE EN PHENOGENOMIQUE SOURIS(2010) |
| Source: |
ISSN: 2045-2322. |
| Publisher Information: |
CCSD; Nature Publishing Group |
| Publication Year: |
2024 |
| Collection: |
Inserm: HAL (Institut national de la santé et de la recherche médicale) |
| Subject Terms: |
Cas9; Genome editing; Mouse; Knockout; [SDV.GEN]Life Sciences [q-bio]/Genetics |
| Description: |
International audience ; 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 3313 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. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| DOI: |
10.1038/s41598-024-72418-8 |
| Availability: |
https://hal.science/hal-04985940; https://hal.science/hal-04985940v1/document; https://hal.science/hal-04985940v1/file/s41598-024-72418-8.pdf; https://doi.org/10.1038/s41598-024-72418-8 |
| Rights: |
https://creativecommons.org/licenses/by-nc-nd/4.0/ ; info:eu-repo/semantics/OpenAccess |
| Accession Number: |
edsbas.8EB530B3 |
| Database: |
BASE |