Introducing the German Mouse Clinic: open access platform for standardized phenotyping

Gailus‐Durner, Valérie; Fuchs, Helmut; Becker, Lore; Bolle, Ines; Brielmeier, Markus; Calzada‐Wack, Julia; Elvert, Ralf; Ehrhardt, Nicole; Dalke, Claudia; Franz, Tobias; Grundner-Culemann, Elisabeth; Hammelbacher, Stephan; Hölter, Sabine M.; Hölzlwimmer, Gabriele; Horsch, Marion; Javaheri, Anahita; Kalaydjiev, Svetoslav; Klempt, Martina; Kling, Eva; Kunder, Sandra; Lengger, Christoph; Lisse, Thomas S.; Mijalski, T.; Naton, Beatrix; Pedersen, Vera; Prehn, Cornelia; Przemeck, Gerhard K. H.; Rácz, Ildikó; Reinhard, Claudia; Reitmeir, Peter; Schneider, Ilka; Schrewe, Anja; Steinkamp, Ralph; Zybill, Christian; Adamski, Jerzy; Beckers, Johannes; Behrendt, Heidrun; Favor, Jack; Graw, Jochen; Heldmaier, Gerhard; Höfler, Heinz; Ivandic, Boris; Katus, Hugo A.; Kirchhof, Paulus; Klingenspor, Martin; Klopstock, Thomas; Lengeling, Andreas; Müller, Werner; Ohl, Frauke; Ollert, Markus; Quintanilla-Martı́nez, Leticia; Schmidt, Jörg; Schulz, Holger; Wolf, Eckhard; Wurst, Wolfgang; Zimmer, Andreas; Busch, Dirk H.; Angelis, Martin Hrabé de

doi:10.1038/nmeth0605-403

Cited by 172 publications

(139 citation statements)

References 6 publications

Supporting

Mentioning

139

Contrasting

Order By: Relevance

“…1). Systemic phenotypic screening of these mice at the German Mouse Clinic (29,30) revealed that they were healthy and showed no significant phenotype under nonstimulated conditions (the data can be accessed at: http://www.europhenome.org/).…”

Section: Resultsmentioning

confidence: 99%

IFIT2 Is an Effector Protein of Type I IFN–Mediated Amplification of Lipopolysaccharide (LPS)-Induced TNF-α Secretion and LPS-Induced Endotoxin Shock

Siegfried

Berchtold

Manncke

et al. 2013

The Journal of Immunology

Self Cite

View full text Add to dashboard Cite

Type I IFN signaling amplifies the secretion of LPS-induced proinflammatory cytokines such as TNF-α or IL-6 and might thus contribute to the high mortality associated with Gram-negative septic shock in humans. The underlying molecular mechanism, however, is ill defined. In this study, we report the generation of mice deficient in IFN-induced protein with tetratricopeptide repeats 2 (Ifit2) and demonstrate that Ifit2 is a critical signaling intermediate for LPS-induced septic shock. Ifit2 expression was significantly upregulated in response to LPS challenge in an IFN-α receptor– and IFN regulatory factor (Irf)9–dependent manner. Also, LPS induced secretion of IL-6 and TNF-α by bone marrow–derived macrophages (BMDMs) was significantly enhanced in the presence of Ifit2. In accordance, Ifit2-deficient mice exhibited significantly reduced serum levels of IL-6 and TNF-α and reduced mortality in an endotoxin shock model. Investigation of the underlying signal transduction events revealed that Ifit2 upregulates Irf3 phosphorylation. In the absence of Irf3, reduced Ifn-β mRNA expression and Ifit2 protein expression after LPS stimulation was found. Also, Tnf-α and Il-6 secretion but not Tnf-α and Il-6 mRNA expression levels were reduced. Thus, IFN-stimulated Ifit2 via enhanced Irf3 phosphorylation upregulates the secretion of proinflammatory cytokines. It thereby amplifies LPS-induced cytokine production and critically influences the outcome of endotoxin shock.

show abstract

Section: Resultsmentioning

confidence: 99%

IFIT2 Is an Effector Protein of Type I IFN–Mediated Amplification of Lipopolysaccharide (LPS)-Induced TNF-α Secretion and LPS-Induced Endotoxin Shock

Siegfried

Berchtold

Manncke

et al. 2013

The Journal of Immunology

Self Cite

View full text Add to dashboard Cite

show abstract

“…Ali14/ϩ mice were analyzed intensively in a systematic phenotyping center, the German Mouse Clinic (28,29). After analyzing more than 240 parameters in this study, we found novel functions of Plcg2 in vivo.…”

Section: Furthermore Additional Phenotypes Of Plcg2mentioning

confidence: 99%

A novel N‐ethyl‐N‐nitrosourea–induced mutation in phospholipase Cγ2 causes inflammatory arthritis, metabolic defects, and male infertility in vitro in a murine model

Abe¹,

Fuchs²,

Boersma³

et al. 2011

Arthritis & Rheumatism

Self Cite

138

View full text Add to dashboard Cite

Objective. It is difficult to identify a single causative factor for inflammatory arthritis because of the multifactorial nature of the disease. This study was undertaken to dissect the molecular complexity of systemic inflammatory disease, utilizing a combined approach of mutagenesis and systematic phenotype screening in a murine model.Methods. In a large-scale N-ethyl-N-nitrosourea mutagenesis project, the Ali14 mutant mouse strain was established because of dominant inheritance of spontaneous swelling and inflammation of the hind paws. Genetic mapping and subsequent candidate gene sequencing were conducted to find the causative gene, and systematic phenotyping of Ali14/؉ mice was performed in the German Mouse Clinic. Results.A novel missense mutation in the phospholipase C␥2 gene (Plcg2) was identified in Ali14/؉ mice. Because of the hyperreactive external entry of calcium observed in cultured B cells and other in vitro experiments, the Ali14 mutation is thought to be a novel gain-of-function allele of Plcg2. Findings from systematic screening of Ali14/؉ mice demonstrated various phenotypic changes: an abnormally high T cell:B cell

show abstract

“…Thus, to gain further insights into the physiological relevance of ADAR2 edits excepting the Q/R site (Gen/ Arg site), we systematically analyzed the phenotype of the double mutant mouse line, employing Gria2 R/R mice as controls, in the German Mouse Clinic (GMC) 2 by determining ϳ320 parameters (17). This comprehensive analysis indeed identified several phenotypic alterations caused by loss of ADAR2, although the RNA targets of ADAR2 that might underlie the phenotypes were not revealed.…”

Section: Gria2mentioning

confidence: 99%

Requirement of the RNA-editing Enzyme ADAR2 for Normal Physiology in Mice

Horsch

Seeburg

Adler

et al. 2011

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

ADAR2, an RNA editing enzyme that converts specific adenosines to inosines in certain pre-mRNAs, often leading to amino acid substitutions in the encoded proteins, is mainly expressed in brain. Of all ADAR2-mediated edits, a single one in the pre-mRNA of the AMPA receptor subunit GluA2 is essential for survival. Hence, early postnatal death of mice lacking ADAR2 is averted when the critical edit is engineered into both GluA2 encoding Gria2 alleles. Adar2 ؊/؊ /Gria2 R/R mice display normal appearance and life span, but the general phenotypic effects of global lack of ADAR2 have remained unexplored. Here we have employed the Adar2 ؊/؊ /Gria2 R/R mouse line, and Gria2 R/R mice as controls, to study the phenotypic consequences of loss of all ADAR2-mediated edits except the critical one in GluA2. Our extended phenotypic analysis covering ϳ320 parameters identified significant changes related to absence of ADAR2 in behavior, hearing ability, allergy parameters and transcript profiles of brain.The most common RNA modification in higher organisms is the enzymatic deamination of specific adenosines to inosine (A-to-I editing), wrought by members of the ADAR protein family (1). ADARs, short for adenosine deaminases acting on RNA, were discovered by their ability to convert in vitro in double-stranded RNA ϳ50% of the adenosines to inosines, thus destabilizing the double-stranded structure (2). Occurring in worms, flies and mammals, these enigmatic enzymes are now known to switch specific adenosines to inosine in mostly primary nuclear transcripts (3-6). A-to-I editing often recodes amino acids within the gene-encoded protein, based on reading inosine as guanosine by the translational machinery, and can remove or create splice acceptor sites (7), thus altering the pattern of RNA splicing. Moreover, editing in 5Ј and 3ЈUTRs and intronic sequence may lead to altered translational efficiency,

show abstract

Introducing the German Mouse Clinic: open access platform for standardized phenotyping

Cited by 172 publications

References 6 publications

IFIT2 Is an Effector Protein of Type I IFN–Mediated Amplification of Lipopolysaccharide (LPS)-Induced TNF-α Secretion and LPS-Induced Endotoxin Shock

IFIT2 Is an Effector Protein of Type I IFN–Mediated Amplification of Lipopolysaccharide (LPS)-Induced TNF-α Secretion and LPS-Induced Endotoxin Shock

A novel N‐ethyl‐N‐nitrosourea–induced mutation in phospholipase Cγ2 causes inflammatory arthritis, metabolic defects, and male infertility in vitro in a murine model

Requirement of the RNA-editing Enzyme ADAR2 for Normal Physiology in Mice

Contact Info

Product

Resources

About