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Aicardi-Goutières syndrome (AGS), a hereditary autoimmune disease, clinically and biochemically overlaps with systemic lupus erythematosus (SLE) and, like SLE, is characterized by spontaneous type I interferon (IFN) production. The finding that defects of intracellular nucleases cause AGS led to the concept that intracellular accumulation of nucleic acids triggers inappropriate production of type I IFN and autoimmunity. AGS can also be caused by defects of SAMHD1, a 3' exonuclease and deoxynucleotide (dNTP) triphosphohydrolase. Human SAMHD1 is an HIV-1 restriction factor that hydrolyzes dNTPs and decreases their concentration below the levels required for retroviral reverse transcription. We show in gene-targeted mice that also mouse SAMHD1 reduces cellular dNTP concentrations and restricts retroviral replication in lymphocytes, macrophages, and dendritic cells. Importantly, the absence of SAMHD1 triggered IFN-β-dependent transcriptional upregulation of type I IFN-inducible genes in various cell types indicative of spontaneous IFN production. SAMHD1-deficient mice may be instrumental for elucidating the mechanisms that trigger pathogenic type I IFN responses in AGS and SLE.
Pubmed ID: 23972988
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Database of the international consortium working together to mutate all protein-coding genes in the mouse using a combination of gene trapping and gene targeting in C57BL/6 mouse embryonic stem (ES) cells. Detailed information on targeted genes is available. The IKMC includes the following programs: * Knockout Mouse Project (KOMP) (USA) ** CSD, a collaborative team at the Children''''s Hospital Oakland Research Institute (CHORI), the Wellcome Trust Sanger Institute and the University of California at Davis School of Veterinary Medicine , led by Pieter deJong, Ph.D., CHORI, along with K. C. Kent Lloyd, D.V.M., Ph.D., UC Davis; and Allan Bradley, Ph.D. FRS, and William Skarnes, Ph.D., at the Wellcome Trust Sanger Institute. ** Regeneron, a team at the VelociGene division of Regeneron Pharmaceuticals, Inc., led by David Valenzuela, Ph.D. and George D. Yancopoulos, M.D., Ph.D. * European Conditional Mouse Mutagenesis Program (EUCOMM) (Europe) * North American Conditional Mouse Mutagenesis Project (NorCOMM) (Canada) * Texas A&M Institute for Genomic Medicine (TIGM) (USA) Products (vectors, mice, ES cell lines) may be ordered from the above programs.
View all literature mentionsTHIS RESOURCE IS NO LONGER IN SERVICE. Documented on August 30,2023. Software for differential gene expression analysis based on the negative binomial distribution. It estimates variance-mean dependence in count data from high-throughput sequencing assays and tests for differential expression.
View all literature mentionsAn Organization portal, Antibody supplier, Service resource,
View all literature mentionsCompany provides laboratories worldwide with analytical instruments and supplies, clinical and diagnostic testing services, consumables, applications and expertise in life sciences and applied chemical markets.
View all literature mentionsCenter that produces knockout mice and carries out high-throughput phenotyping of each line in order to determine function of every gene in mouse genome. These mice will be preserved in repositories and made available to scientific community representing valuable resource for basic scientific research as well as generating new models for human diseases.
View all literature mentionsMus musculus with name C57BL/6J from IMSR.
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