ArticleJournal of autoimmunity2017
DNase-active TREX1 frame-shift mutants induce serologic autoimmunity in mice.
Article in Journal of autoimmunity, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
23 citing papers in PubMed, 1 synthesis or guideline pooled it, 39 citations in OpenAlex.
- Systemic Lupus Erythematosus and DNA Degradation and Elimination Defects.Frontiers in immunology · 2019Pooled it
- First case ofFrontiers in immunology · 2026Article
- Mouse models of type I interferonopathies.Human molecular genetics · 2025Review
- Misdirected yet intact TREX1 exonuclease activity causes human cerebral and systemic small vessel disease.Brain : a journal of neurology · 2025Article
- The pathogenesis of cerebral small vessel disease and vascular cognitive impairment.Physiological reviews · 2025Review
- Exploring targeted therapy in retinal vasculopathy with cerebral leukoencephalopathy: a case report and review of literature.Frontiers in immunology · 2025Review
- Inherited C-terminal TREX1 variants disrupt homology-directed repair to cause senescence and DNA damage phenotypes in Drosophila, mice, and humans.Nature communications · 2024Article
- Disulfiram ameliorates STING/MITA-dependent inflammation and autoimmunity by targeting RNF115.Cellular & molecular immunology · 2024Article
- Modeling of age-related neurological disease: utility of zebrafish.Frontiers in aging neuroscience · 2024Review
- Stereoselective synthesis of photoactivatable Man(β1,4)GlcNAc-based bioorthogonal probes.Tetrahedron letters · 2023Article
- A path towards personalized medicine for autoinflammatory and related diseases.Nature reviews. Rheumatology · 2023Review
- Case report: JAK inhibition as promising treatment option of fatal RVCLS due toFrontiers in neurology · 2023Article
- Intracellular Sensing of DNA in Autoinflammation and Autoimmunity.Arthritis & rheumatology (Hoboken, N.J.) · 2022Review
- Exonucleases: Degrading DNA to Deal with Genome Damage, Cell Death, Inflammation and Cancer.Cells · 2022Review
- Retinal Vasculopathy with Cerebral Leukoencephalopathy and Systemic manifestations (RVCL-S): An update on basic science and clinical perspectives.Cerebral circulation - cognition and behavior · 2022Article
- High clinical heterogeneity in a Chinese pedigree of retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations (RVCL-S).Orphanet journal of rare diseases · 2021Article
- cGAS-STING Pathway Does Not Promote Autoimmunity in Murine Models of SLE.Frontiers in immunology · 2021Article
- Article
- The cGAS-STING pathway: The role of self-DNA sensing in inflammatory lung disease.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2020Review
- TREX1 - Apex predator of cytosolic DNA metabolism.DNA repair · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 7 institutions in 2 countries.
Funding
Abstract
TREX1/DNASE III, the most abundant 3'-5' DNA exonuclease in mammalian cells, is tail-anchored on the endoplasmic reticulum (ER). Mutations at the N-terminus affecting TREX1 DNase activity are associated with autoimmune and inflammatory conditions such as Aicardi-Goutières syndrome (AGS). Mutations in the C-terminus of TREX1 cause loss of localization to the ER and dysregulation of oligosaccharyltransferase (OST) activity, and are associated with retinal vasculopathy with cerebral leukodystrophy (RVCL) and in some cases with systemic lupus erythematosus (SLE). Here we investigate mice with conditional expression of the most common RVCL mutation, V235fs, and another mouse expressing a conditional C-terminal mutation, D272fs, associated with a case of human SLE. Mice homozygous for either mutant allele express the encoded human TREX1 truncations without endogenous mouse TREX1, and both remain DNase active in tissues. The two mouse strains are similar phenotypically without major signs of retinal, cerebral or renal disease but exhibit striking elevations of autoantibodies in the serum. The broad range of autoantibodies is primarily against non-nuclear antigens, in sharp contrast to the predominantly DNA-related autoantibodies produced by a TREX1-D18N mouse that specifically lacks DNase activity. We also found that treatment with an OST inhibitor, aclacinomycin, rapidly suppressed autoantibody production in the TREX1 frame-shift mutant mice. Together, our study presents two new mouse models based on TREX1 frame-shift mutations with a unique set of serologic autoimmune-like phenotypes.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.