Characterization of samhd1 Morphant Zebrafish Recapitulates Features of the Human Type I Interferonopathy Aicardi-Goutières Syndrome
| Autor: | Yanick J. Crow, Catherine Morrissey, Leo A. H. Zeef, Emma M. Jenkinson, Gillian I. Rice, Valérie Briolat, Jean-Pierre Levraud, David Gent, Paul R. Kasher |
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| Přispěvatelé: | Manchester Centre for Genomic Medicine (MCGM), Manchester Academic Health Science Centre (MAHSC), University of Manchester [Manchester]-University of Manchester [Manchester]-Faculty of Biology, Medicine and Health [Manchester, UK], University of Manchester [Manchester]-Manchester University NHS Foundation Trust (MFT)-St Mary's Hospital Manchester, Macrophages et Développement de l'Immunité, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Faculty of Life Sciences [Manchester], University of Manchester [Manchester], Laboratory of neurogenetics and neuroinflammation (Equipe Inserm U1163), Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), This work was supported by the Newlife Foundation, the Natalie Kate Moss Trust, the European Research Council (GA 309449: fellowship to Y.J.C.), and state subsidies managed by the National Research Agency (France) under the 'Investments for the Future' program bearing the reference ANR-10-IAHU-01 and the 'Zebraflam' program bearing the reference ANR-10-MIDI-009., We thank Dr. Adam Hurlstone and Dr. Shane Herbert for sharing zebrafish strains and equipment and Mike Jackson at the University of Manchester Flow Cytometry Facility for technical support., ANR-10-MIDI-0009,ZebraFlam,Signaux et cellules de la réponse inflammatoire: suivi en temps réel chez un vertébré entier, le danio zébré(2010), Manchester Centre for Genomic Medicine [Manchester, UK] (MCGM), St Mary's Hospital Manchester-Manchester Academic Health Science Centre (MAHSC), University of Manchester [Manchester]-University of Manchester [Manchester]-Manchester University NHS Foundation Trust (MFT)-Faculty of Biology, Medicine and Health [Manchester, UK], Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Briolat, Valérie, MECANISMES INTEGRES DE L'INFLAMMATION - Signaux et cellules de la réponse inflammatoire: suivi en temps réel chez un vertébré entier, le danio zébré - - ZebraFlam2010 - ANR-10-MIDI-0009 - MI2 - VALID |
| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
MESH: Interferon Type I
Adenosine Deaminase MESH: Sequence Homology Amino Acid [SDV]Life Sciences [q-bio] ved/biology.organism_classification_rank.species MESH: Microscopy Fluorescence MESH: Amino Acid Sequence MESH: Acid Anhydride Hydrolases [SDV.IMM.II]Life Sciences [q-bio]/Immunology/Innate immunity Cerebral Ventricles Animals Genetically Modified MESH: Reverse Transcriptase Polymerase Chain Reaction MESH: Gene Expression Regulation Developmental Immunology and Allergy MESH: Animals MESH: Interferons Zebrafish MESH: Adenosine Deaminase Gene knockdown Reverse Transcriptase Polymerase Chain Reaction Gene Expression Regulation Developmental MESH: Rhombencephalon MESH: SAM Domain and HD Domain-Containing Protein 1 Acid Anhydride Hydrolases 3. Good health Cell biology [SDV] Life Sciences [q-bio] Gene Knockdown Techniques Interferon Type I [SDV.IMM]Life Sciences [q-bio]/Immunology MESH: Immunity Innate Intracranial Hemorrhages MESH: Intracranial Hemorrhages [SDV.IMM] Life Sciences [q-bio]/Immunology Blotting Western Molecular Sequence Data Immunology MESH: Zebrafish Proteins Biology Nervous System Malformations MESH: Nervous System Malformations SAM Domain and HD Domain-Containing Protein 1 MESH: Animals Genetically Modified Autoimmune Diseases of the Nervous System Immune system medicine Animals Humans MESH: Blotting Western Amino Acid Sequence Model organism MESH: Zebrafish [SDV.IMM.II] Life Sciences [q-bio]/Immunology/Innate immunity Loss function Innate immune system MESH: Humans MESH: Molecular Sequence Data Sequence Homology Amino Acid ved/biology Morphant Zebrafish Proteins medicine.disease biology.organism_classification MESH: Gene Knockdown Techniques Immunity Innate MESH: Autoimmune Diseases of the Nervous System Rhombencephalon Disease Models Animal Microscopy Fluorescence Aicardi–Goutières syndrome MESH: Cerebral Ventricles Interferons MESH: Disease Models Animal |
| Zdroj: | Journal of Immunology Journal of Immunology, Publisher : Baltimore : Williams & Wilkins, c1950-. Latest Publisher : Bethesda, MD : American Association of Immunologists, 2015, 194 (6), pp.2819-2825. ⟨10.4049/jimmunol.1403157⟩ Journal of Immunology, 2015, 194 (6), pp.2819-2825. ⟨10.4049/jimmunol.1403157⟩ |
| ISSN: | 0022-1767 1550-6606 |
| DOI: | 10.4049/jimmunol.1403157⟩ |
| Popis: | In humans, loss of function mutations in the SAMHD1 (AGS5) gene cause a severe form of Aicardi-Goutières syndrome (AGS), an inherited inflammatory-mediated encephalopathy characterized by increased type I IFN activity and upregulation of IFN-stimulated genes (ISGs). In particular, SAMHD1-related AGS is associated with a distinctive cerebrovascular pathology that commonly leads to stroke. Although inflammatory responses are observed in immune cells cultured from Samhd1 null mouse models, these mice are physically healthy, specifically lacking a brain phenotype. We have investigated the use of zebrafish as an alternative system for generating a clinically relevant model of SAMHD1-related AGS. Using temporal gene knockdown of zebrafish samhd1, we observe hindbrain ventricular swelling and brain hemorrhage. Furthermore, loss of samhd1 or of another AGS-associated gene, adar, leads to a significant upregulation of innate immune-related genes and an increase in the number of cells expressing the zebrafish type I IFN ifnphi1. To our knowledge, this is the first example of an in vivo model of AGS that recapitulates features of both the innate immune and neurological characteristics of the disease. The phenotypes associated with loss of samhd1 and adar suggest a function of these genes in controlling innate immune processes conserved to zebrafish, thereby also contributing to our understanding of antiviral signaling in this model organism. |
| Databáze: | OpenAIRE |
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