Genome wide conditional mouse knockout resources

Kaloff, Cornelia; Anastassiadis, Konstantinos; Ayadi, Abdel; Baldock, Richard; Beig, Joachim; Birling, Marie‐Christine; Bradley, Allan; Brown, S. D. M.; Bürger, Antje; Bushell, Wendy; Chiani, Francesco; Collins, Francis S.; Doe, Brendan; Eppig, Janan T.; Finnell, Richard H.; Fletcher, Colin; Flicek, Paul; Fray, Martin; Friedel, Roland H.; Gambadoro, Alessia; Gates, Hilary; Hansen, Jens; Hérault, Yann; Hicks, Geoffrey; Hörlein, Andreas; Angelis, Martin Hrabé de; Iyer, Vivek; Jong, Pieter J. de; Koscielny, Gautier; Kühn, Ralf; Liu, P.; Lloyd, Kevin C K; Lopez, Robert; Marschall, Susan; Martínez, S.; McKerlie, Colin; Meehan, Terrence F.; Melchner, Harald von; Moore, Mark; Murray, Stephen A.; Nagy, András; Nutter, Lauryl M. J.; Pombero, Ana; Prosser, Haydn M.; Ramirez-Solis, Ramiro; Ringwald, Martin; Rosen, Barry; Rosenthal, Nadia; Rossant, Janet; Noppinger, Patricia Ruiz; Ryder, Edward; Skarnes, William C.; Schick, Joel; Schnütgen, Frank; Schofield, Paul N.; Seisenberger, Claudia; Selloum, Mohammed; Smedley, Damian; Simpson, Elizabeth M.; Stewart, A. Francis; Teboul, Lydia; Valentini, Giovanna; Valenzuela, David M.; West, Anthony P.; Wurst, Wolfgang

doi:10.1016/j.ddmod.2017.08.002

Cited by 4 publications

(7 citation statements)

References 51 publications

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“…To determine the role of different genes within a natural Qa2 region, we established the different haplotypes on a shared B6N genetic background. The mouse strain B6N has been used to produced mostly conditional mutations of more than 1.85x10 4 genes, and are available to the research community (Kaloff et al 2016). It is also considered to be Qa2 hi , encoding by H2-Q6/Q8, and Q7/Q9 genes (Ohtsuka et al 2008).…”

Section: J O U R N a L P R E -P R O O Fmentioning

confidence: 99%

Natural Loss-of-Function Mutations in Qa2 and NCF1 Cause the Spread of Mannan-Induced Psoriasis

Zhong

Holmdahl

2021

Journal of Investigative Dermatology

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This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

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Section: J O U R N a L P R E -P R O O Fmentioning

confidence: 99%

Natural Loss-of-Function Mutations in Qa2 and NCF1 Cause the Spread of Mannan-Induced Psoriasis

Zhong

Holmdahl

2021

Journal of Investigative Dermatology

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“…Using high-throughput gene trapping and targeting, the International Knockout Mouse (IKMC) and International Mouse Phenotyping (IMPC) consortia have created an unprecedented resource comprising mutant ES cell lines harboring mutations in ∼18,500 unique PCGs. Of these, over 5000 have been converted into mice and subjected to high-throughput phenotyping (www.mousephenotype.org) (Bradley et al, 2012;Collins et al, 2007;Kaloff et al, 2016;Lloyd et al, 2020;Rosen et al, 2015;Skarnes et al, 2011Skarnes et al, , 2004. Moreover, genes thus far inaccessible by targeting or trapping are now being addressed individually using CRISPR/Cas9 technology (Brandl et al, 2015;Wefers et al, 2017).…”

Section: Introductionmentioning

confidence: 99%

Mutant non-coding RNA resource in mouse embryonic stem cells

Hansen

Melchner

Wurst

2021

Disease Models &Amp; Mechanisms

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Gene trapping is a high-throughput approach that has been used to introduce insertional mutations into the genome of mouse embryonic stem (ES) cells. It is performed with generic gene trap vectors that simultaneously mutate and report the expression of the endogenous gene at the site of insertion and provide a DNA sequence tag for the rapid identification of the disrupted gene. Large-scale international efforts assembled a gene trap library of 566,554 ES cell lines with single gene trap integrations distributed throughout the genome. Here, we re-investigated this unique library and identified mutations in 2202 non-coding RNA (ncRNA) genes, in addition to mutations in 12,078 distinct protein-coding genes. Moreover, we found certain types of gene trap vectors preferentially integrating into genes expressing specific long non-coding RNA (lncRNA) biotypes. Together with all other gene-trapped ES cell lines, lncRNA gene-trapped ES cell lines are readily available for functional in vitro and in vivo studies.

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“…TO understand gene function, the cre/loxP conditional system is the most powerful available for temporal and spatial control of expression in mouse (Hoess et al 1986; Bradley et al 2012; Murray et al 2012; Rosen et al 2015; Kaloff et al 2017). Large-scale efforts such as the International Knockout Mouse Consortium (IKMC) have targeted nearly 18,500 genes in mouse embryonic stem cells (ESCs), which have conditional potential in mice, dependent upon inactivation of their alleles by Cre recombinase catalyzing site-specific DNA recombination between 34 bp loxP recognition sites (Kaloff et al 2017). The IKMC has recently pointed out that “ideally, cre-driver mice should be at hand for every adult cell type to dissect pleiotropic gene functions related to human disease” (Kaloff et al 2017).…”

mentioning

confidence: 99%

“…Large-scale efforts such as the International Knockout Mouse Consortium (IKMC) have targeted nearly 18,500 genes in mouse embryonic stem cells (ESCs), which have conditional potential in mice, dependent upon inactivation of their alleles by Cre recombinase catalyzing site-specific DNA recombination between 34 bp loxP recognition sites (Kaloff et al 2017). The IKMC has recently pointed out that “ideally, cre-driver mice should be at hand for every adult cell type to dissect pleiotropic gene functions related to human disease” (Kaloff et al 2017). To that end, for spatial and temporal control of gene inactivation, the research community requires: (1) more cre recombinase expressing transgenic mouse strains (cre-drivers), and (2) cre-drivers that restrict expression to specific cell types.…”

mentioning

confidence: 99%

“…A large-scale effort, employing several different strategies, has been underway to produce both inducible and constitutive cre-drivers for use with the IKMC conditional alleles (Murray et al 2012; Rosen et al 2015; Kaloff et al 2017). These span from generation of ESCs only, through animals, to extensively characterized cre-driver strains; the latter being the most immediately valuable to the community.…”

mentioning

confidence: 99%

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Twenty-Seven Tamoxifen-Inducible iCre-Driver Mouse Strains for Eye and Brain, Including Seventeen Carrying a New Inducible-First Constitutive-Ready Allele

et al. 2019

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To understand gene function, the cre/loxP conditional system is the most powerful available for temporal and spatial control of expression in mouse. However, the research community requires more cre recombinase expressing transgenic mouse strains (cre-drivers) that restrict expression to specific cell types. To address these problems, a high-throughput method for large-scale production that produces high-quality results is necessary. Further, endogenous promoters need to be chosen that drive cell type specific expression, or we need to further focus the expression by manipulating the promoter. Here we test the suitability of using knock-ins at the docking site 5′ of Hprt for rapid development of numerous cre-driver strains focused on expression in adulthood, using an improved cre tamoxifen inducible allele (icre/ERT2), and testing a novel inducible-first, constitutive-ready allele (icre/f3/ERT2/f3). In addition, we test two types of promoters either to capture an endogenous expression pattern (MaxiPromoters), or to restrict expression further using minimal promoter element(s) designed for expression in restricted cell types (MiniPromoters). We provide new cre-driver mouse strains with applicability for brain and eye research. In addition, we demonstrate the feasibility and applicability of using the locus 5′ of Hprt for the rapid generation of substantial numbers of cre-driver strains. We also provide a new inducible-first constitutive-ready allele to further speed cre-driver generation. Finally, all these strains are available to the research community through The Jackson Laboratory.

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Genome wide conditional mouse knockout resources

Cited by 4 publications

References 51 publications

Natural Loss-of-Function Mutations in Qa2 and NCF1 Cause the Spread of Mannan-Induced Psoriasis

Natural Loss-of-Function Mutations in Qa2 and NCF1 Cause the Spread of Mannan-Induced Psoriasis

Mutant non-coding RNA resource in mouse embryonic stem cells

Twenty-Seven Tamoxifen-Inducible iCre-Driver Mouse Strains for Eye and Brain, Including Seventeen Carrying a New Inducible-First Constitutive-Ready Allele

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