A resource of targeted mutant mouse lines for 5,061 genes

Birling, Marie‐Christine; Yoshiki, Atsushi; Adams, David J.; Ayabe, Shin-ichi; Beaudet, Arthur L.; Bottomley, Joanna; Bradley, Allan; Brown, Steve; Bürger, Antje; Bushell, Wendy; Chiani, Francesco; Chin, Hsian-Jean; Christou, Skevoulla; Codner, Gemma; DeMayo, Francesco J.; Dickinson, Mary E.; Doe, Brendan; Donahue, Leah Rae; Fray, Martin; Gambadoro, Alessia; Gao, Xiang; Gertsenstein, Marina; Gomez-Segura, Alba; Goodwin, Leslie O.; Heaney, Jason D.; Hérault, Yann; Angelis, Martin Hrabě de; Jiang, Si‐Tse; Justice, Monica J.; Kašpárek, Petr; King, Ruairidh; Kühn, Ralf; Lee, Ho; Lee, Young Jae; Liu, Zhiwei; Lloyd, Kevin C K; Lorenzo, Isabel; Mallon, Ann‐Marie; McKerlie, Colin; Mammano, Fabio; Muñoz-Fuentes, Violeta; Newman, Stuart; Nutter, Lauryl M. J.; Oh, Goo Taeg; Pavlovic, Guillaume; Ramírez‐Solís, Ramiro; Rosen, Barry; Ryder, Edward J.; Schick, Joel; Seavitt, John R.; Sedláček, Radislav; Seisenberger, Claudia; Seong, Je Kyung; Skarnes, William C.; Sorg, Tania; Steel, Karen P.; Tamura, Masahito; Tocchini‐Valentini, Glauco P.; Wang, Chi-Kuang Leo; Wardle‐Jones, Hannah; Wattenhofer‐Donzé, Marie; Wells, Sara; Wiles, Michael V.; Willis, Brandon; Wood, Joshua A.; Wurst, Wolfgang; Xu, Ying; Gallegos, Juan; Green, Jennie R.; Bohat, Ritu; Zimmel, Katie; Pereira, Monica; MacMaster, Suzanne; Tondat, Sandra; Wei, Linda; Carroll, Tracy; Cabezas, Jorge; Fan-Lan, Qing; Jacob, Elsa; Creighton, Amie; Castellanos-Penton, Patricia; Danisment, Ozge; Clarke, Shannon; Joeng, Joanna; Kelly, Deborah; To, Christine; Bruggen, Rebekah van; Gailus‐Durner, Valérie; Fuchs, Helmut; Marschall, Susan; Dunst, Stefanie; Romberger, Markus; Rey, Bernhard; Fessele, Sabine; Gormanns, Philipp; Friedel, Roland H.; Kaloff, Cornelia; Hörlein, Andreas; Teichmann, Sandy; Tasdemir, Adriane; Krause, Heidi; German, Dorota; Könitzer, Anne; Weber, Sarah; Beig, Joachim; McKay, Matthew J.; Bedigian, Richard; Dion, Stephanie; Kutny, Peter M.; Kelmenson, Jennifer A.; Perry, Emily; Nguyen-Bresinsky, Dong; Seluke, Audrie; Leach, Timothy; Perkins, Sara; Slater, Amanda; Petit, Michaela; Urban, Rachel; Kales, Susan; DaCosta, Michael; McFarland, Michael; Palazola, Rick; Peterson, Kevin A.; Svenson, Karen L.; Braun, Robert E.; Taft, Robert A.; Rhue, Mark; Garay, José Luis; Clary, Dave; Araiza, Renee; Grimsrud, Kristin N; Bower, Lynette; Anchell, Nicole L.; Jager, Kayla M.; Young, Diana L.; Dao, Phuong; Gardiner, Wendy; Bell, Toni; Kenyon, Janet; Stewart, Michelle; Lynch, Denise B.; Loeffler, Jorik; Caulder, Adam; Hillier, Rosie; Quwailid, Mohamed M.; Zaman, Rumana; Santos, Luís; Obata, Yuichi; Iwama, Mizuho; Nakata, Hatsumi; Hashimoto, Tomomi; Kadota, Masayo; Masuya, Hiroshi; Tanaka, Nobuhiko; Miura, Ikuo; Yamada, Ikuko; Furuse, Tamio; Selloum, Mohammed; Jacquot, Sylvie; Ayadi, Abdel; Ali-Hadji, Dalila; Charles, Philippe; Marchand, E.; Amri, Amal El; Kujath, Christelle; Fougerolle, Jean-Victor; Mellul, Peggy; Legeay, Sandrine; Vasseur, Laurent; Moro, Anne-Isabelle; Lorentz, Romain; Schaeffer, Laurence; Dreyer, Dominique; Erbs, Valérie; Eisenmann, Benjamin; Rossi, Giovanni Battista; Luppi, Laurence; Mertz, Annelyse; Jeanblanc, Amélie; Grau, Evelyn; Sinclair, Caroline; Brown, Ellen; Kundi, Helen; Madich, Alla; Woods, Mike; Pearson, Laila; Mayhew, Danielle; Griggs, Nicola; Houghton, Richard; Bussell, James; Ingle, Catherine; Valentini, Sara; Gleeson, Diane; Sethi, Debarati; Bayzetinova, Tanya; Burvill, Jonathan; Habib, Bishoy; Weavers, Lauren; Maswood, Ryea; Miklejewska, Evelina; Cook, Ross; Platte, Radka; Price, Stacey; Vyas, Sapna; Collinson, Adam; Hardy, Matt; Dalvi, Priya; Iyer, Vivek; West, Tony; Thomas, Mark; Mujica, Alejandro O.; Sins, Elodie; Barrett, Daniel M.; Dobbie, Michael S.; Grobler, Anne; Loots, Glaudina; Hayeshi, Rose; Scholtz, Liezl-Marie; Bester, Cor; Pheiffer, Wihan; Venter, Kobus; Bosch, Fátima; Teboul, Lydia; Murray, Stephen A.

doi:10.1038/s41588-021-00825-y

Cited by 66 publications

(57 citation statements)

References 31 publications

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“…Together with the MMRRC these organizations represent a large share of commonly used entry points for identification of mouse models. For example, all Centers participate in the archiving and distribution of knockout mouse models generated by the NIH Knockout Mouse Production and Phenotyping (KOMP2) Project ( https://commonfund.nih.gov/komp2 ) (Bradley 2012 ; Birling 2021 ). In coordination with its global partners, KOMP2 is working to produce and phenotype mouse lines of male and female mice expressing null alleles for every human orthologous gene in the mouse genome.…”

Section: Enagagment and Interaction With Complementary Organizationsmentioning

confidence: 99%

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The Mutant Mouse Resource and Research Center (MMRRC): the NIH-supported National Public Repository and Distribution Archive of Mutant Mouse Models in the USA

et al. 2021

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The Mutant Mouse Resource and Research Center (MMRRC) Program is the pre-eminent public national mutant mouse repository and distribution archive in the USA, serving as a national resource of mutant mice available to the global scientific community for biomedical research. Established more than two decades ago with grants from the National Institutes of Health (NIH), the MMRRC Program supports a Consortium of regionally distributed and dedicated vivaria, laboratories, and offices (Centers) and an Informatics Coordination and Service Center (ICSC) at three academic teaching and research universities and one non-profit genetic research institution. The MMRRC Program accepts the submission of unique, scientifically rigorous, and experimentally valuable genetically altered and other mouse models donated by academic and commercial scientists and organizations for deposition, maintenance, preservation, and dissemination to scientists upon request. The four Centers maintain an archive of nearly 60,000 mutant alleles as live mice, frozen germplasm, and/or embryonic stem (ES) cells. Since its inception, the Centers have fulfilled 13,184 orders for mutant mouse models from 9591 scientists at 6626 institutions around the globe. Centers also provide numerous services that facilitate using mutant mouse models obtained from the MMRRC, including genetic assays, microbiome analysis, analytical phenotyping and pathology, cryorecovery, mouse husbandry, infectious disease surveillance and diagnosis, and disease modeling. The ICSC coordinates activities between the Centers, manages the website (mmrrc.org) and online catalog, and conducts communication, outreach, and education to the research community. Centers preserve, secure, and protect mutant mouse lines in perpetuity, promote rigor and reproducibility in scientific experiments using mice, provide experiential training and consultation in the responsible use of mice in research, and pursue cutting edge technologies to advance biomedical studies using mice to improve human health. Researchers benefit from an expansive list of well-defined mouse models of disease that meet the highest standards of rigor and reproducibility, while donating investigators benefit by having their mouse lines preserved, protected, and distributed in compliance with NIH policies.

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Section: Enagagment and Interaction With Complementary Organizationsmentioning

confidence: 99%

“…nih. gov/ komp2) (Bradley 2012;Birling 2021). In coordination with its global partners, KOMP2 is working to produce and phenotype mouse lines of male and female mice expressing null alleles for every human orthologous gene in the mouse genome.…”

Section: Enagagment and Interaction With Complementary Organizationsmentioning

confidence: 99%

The Mutant Mouse Resource and Research Center (MMRRC): the NIH-supported National Public Repository and Distribution Archive of Mutant Mouse Models in the USA

et al. 2021

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“…Phenotype information was retrieved from UniProtKB and the model organism databases for the organisms in which the protein is conserved: MGI ( 37 ), Zfin ( 38 ), Xenbase ( 39 ), Flybase ( 40 ), Wormbase ( 41 ), SGD and TAIR/Araport. This information was complemented with information from the literature and the International Mouse Phenotype Consortium (IMPC) ( 42 ).…”

Section: Methodsmentioning

confidence: 99%

Functionathon: a manual data mining workflow to generate functional hypotheses for uncharacterized human proteins and its application by undergraduate students

et al. 2021

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About 10% of human proteins have no annotated function in protein knowledge bases. A workflow to generate hypotheses for the function of these uncharacterized proteins has been developed, based on predicted and experimental information on protein properties, interactions, tissular expression, subcellular localization, conservation in other organisms, as well as phenotypic data in mutant model organisms. This workflow has been applied to seven uncharacterized human proteins (C6orf118, C7orf25, CXorf58, RSRP1, SMLR1, TMEM53 and TMEM232) in the frame of a course-based undergraduate research experience named Functionathon organized at the University of Geneva to teach undergraduate students how to use biological databases and bioinformatics tools and interpret the results. C6orf118, CXorf58 and TMEM232 were proposed to be involved in cilia-related functions; TMEM53 and SMLR1 were proposed to be involved in lipid metabolism and C7orf25 and RSRP1 were proposed to be involved in RNA metabolism and gene expression. Experimental strategies to test these hypotheses were also discussed. The results of this manual data mining study may contribute to the project recently launched by the Human Proteome Organization (HUPO) Human Proteome Project aiming to fill gaps in the functional annotation of human proteins. Database URL: http://www.nextprot.org

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“…The Sanger Institute Mouse Genetics Project was a large-scale programme that generated and screened mice carrying knockdown alleles created by the KOMP (Knock Out Mouse Programme) and EUCOMM (European Conditional Mouse Mutagenesis) programmes [7][8][9] . Each mouse line established carried a single targeted knockout allele, and animals from each line were put through a wide range of phenotyping tests 9 .…”

Section: Introductionmentioning

confidence: 99%

Collateral damage: Identification and characterisation of spontaneous mutations causing deafness from a targeted knockout programme

Lewis

Ingham

Chen

et al. 2021

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Mice carrying targeted mutations are important for investigating gene function and the role of genes in disease, but the process of culturing embryonic stem cells during the making of a targeted allele offers opportunities for spontaneous mutations to arise. Identifying spontaneous mutations relies on the detection of phenotypes segregating independently of targeted alleles, and many phenotypes are easy to miss if not specifically looked for. Here we present data from a large, targeted knockout programme in which mice were analysed through a phenotyping pipeline. Twenty-five lines out of 1311 displayed different deafness phenotypes that did not segregate with the targeted allele. We have identified 8 different mutations causing deafness in 16 of these 25 lines and characterised the resulting phenotypes. Our data show that spontaneous mutations with observable effects on phenotype are a common side effect of intensive breeding programmes, including those underlying targeted mutation programmes.

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A resource of targeted mutant mouse lines for 5,061 genes

Cited by 66 publications

References 31 publications

The Mutant Mouse Resource and Research Center (MMRRC): the NIH-supported National Public Repository and Distribution Archive of Mutant Mouse Models in the USA

The Mutant Mouse Resource and Research Center (MMRRC): the NIH-supported National Public Repository and Distribution Archive of Mutant Mouse Models in the USA

Functionathon: a manual data mining workflow to generate functional hypotheses for uncharacterized human proteins and its application by undergraduate students

Collateral damage: Identification and characterisation of spontaneous mutations causing deafness from a targeted knockout programme

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