Mice, microbes and models of infection

German Research Centre for Biotechnology (GBF), Mascheroder Weg 1, D-38124 Braunschweig, Germany
Nature Reviews Genetics (Impact Factor: 36.98). 04/2003; 4(3):195-205. DOI: 10.1038/nrg1019
Source: PubMed


We urgently need animal models to study infectious disease. Mice are susceptible to a similar range of microbial infections as humans. Marked differences between inbred strains of mice in their response to pathogen infection can be exploited to analyse the genetic basis of infections. In addition, the genetic tools that are available in the laboratory mouse, and new techniques to monitor the expression of bacterial genes in vivo, make it the principal experimental animal model for studying mechanisms of infection and immunity.

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    • "More than 200 commercially available, phylogenetically diverse inbred mouse strains that contain enough genetic diversity to identify major differences in response to a specific infection are available [14]. These resources have been extensively used to identify cellular and molecular factors that may contribute to different disease pathogenesis and to analyze the effect of multiple contributing genetic loci influencing disease phenotype with different pathogens [10], [12], [15], [16][17]. Successful stories included gene mapping for a large number of pathogens like bacteria (e.g. "
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    PLoS ONE 09/2014; 9(9):e106873. DOI:10.1371/journal.pone.0106873 · 3.23 Impact Factor
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    • "Extensive transcriptional regulation underlies macrophage responses to toll-like receptor (TLR) signaling [1]. Differential transcriptional activity in response to TLR signaling tailors macrophage responses to different pathogens [2-8]. See [9] for a review. "
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    ABSTRACT: As part of a National Institute of Allergy and Infectious Diseases funded collaborative project, we have performed over 150 microarray experiments measuring the response of C57/BL6 mouse bone marrow macrophages to toll-like receptor stimuli. These microarray expression profiles are available freely from our project web site http://www.innateImmunity-systemsbiology.org. Here, we report the development of a database of computationally predicted transcription factor binding sites and related genomic features for a set of over 2000 murine immune genes of interest. Our database, which includes microarray co-expression clusters and a host of web-based query, analysis and visualization facilities, is available freely via the internet. It provides a broad resource to the research community, and a stepping stone towards the delineation of the network of transcriptional regulatory interactions underlying the integrated response of macrophages to pathogens. We constructed a database indexed on genes and annotations of the immediate surrounding genomic regions. To facilitate both gene-specific and systems biology oriented research, our database provides the means to analyze individual genes or an entire genomic locus. Although our focus to-date has been on mammalian toll-like receptor signaling pathways, our database structure is not limited to this subject, and is intended to be broadly applicable to immunology. By focusing on selected immune-active genes, we were able to perform computationally intensive expression and sequence analyses that would currently be prohibitive if applied to the entire genome. Using six complementary computational algorithms and methodologies, we identified transcription factor binding sites based on the Position Weight Matrices available in TRANSFAC. For one example transcription factor (ATF3) for which experimental data is available, over 50% of our predicted binding sites coincide with genome-wide chromatin immnuopreciptation (ChIP-chip) results. Our database can be interrogated via a web interface. Genomic annotations and binding site predictions can be automatically viewed with a customized version of the Argo genome browser. We present the Innate Immune Database (IIDB) as a community resource for immunologists interested in gene regulatory systems underlying innate responses to pathogens. The database website can be freely accessed at http://db.systemsbiology.net/IIDB.
    BMC Immunology 02/2008; 9(1):7. DOI:10.1186/1471-2172-9-7 · 2.48 Impact Factor
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    • "The utility of employing the mouse as a model for human disease is well documented [6-9]. Traditional methods of site-directed in vivo mutagenesis are tedious and require prior knowledge of gene function and location [10]. "
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    BMC Bioinformatics 03/2004; 5(1):11. DOI:10.1186/1471-2105-5-11 · 2.58 Impact Factor
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