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Mice deficient in NRROS show abnormal microglial development and neurological disorders.
Wong, Kit; Noubade, Rajkumar; Manzanillo, Paolo; Ota, Naruhisa; Foreman, Oded; Hackney, Jason A; Friedman, Brad A; Pappu, Rajita; Scearce-Levie, Kimberly; Ouyang, Wenjun.
Afiliación
  • Wong K; Department of Immunology, Genentech, South San Francisco, California, USA.
  • Noubade R; Department of Immunology, Genentech, South San Francisco, California, USA.
  • Manzanillo P; Department of Immunology, Genentech, South San Francisco, California, USA.
  • Ota N; Department of Immunology, Genentech, South San Francisco, California, USA.
  • Foreman O; Department of Pathology, Genentech, South San Francisco, California, USA.
  • Hackney JA; Department of Bioinformatics and Computational Biology, Genentech, South San Francisco, California, USA.
  • Friedman BA; Department of Bioinformatics and Computational Biology, Genentech, South San Francisco, California, USA.
  • Pappu R; Department of Immunology, Genentech, South San Francisco, California, USA.
  • Scearce-Levie K; Department of Neuroscience, Genentech, South San Francisco, California, USA.
  • Ouyang W; Department of Immunology, Genentech, South San Francisco, California, USA.
Nat Immunol ; 18(6): 633-641, 2017 06.
Article en En | MEDLINE | ID: mdl-28459434
Microglia and other tissue-resident macrophages within the central nervous system (CNS) have essential roles in neural development, inflammation and homeostasis. However, the molecular pathways underlying their development and function remain poorly understood. Here we report that mice deficient in NRROS, a myeloid-expressed transmembrane protein in the endoplasmic reticulum, develop spontaneous neurological disorders. NRROS-deficient (Nrros-/-) mice show defects in motor functions and die before 6 months of age. Nrros-/- mice display astrogliosis and lack normal CD11bhiCD45lo microglia, but they show no detectable demyelination or neuronal loss. Instead, perivascular macrophage-like myeloid cells populate the Nrros-/- CNS. Cx3cr1-driven deletion of Nrros shows its crucial role in microglial establishment during early embryonic stages. NRROS is required for normal expression of Sall1 and other microglial genes that are important for microglial development and function. Our study reveals a NRROS-mediated pathway that controls CNS-resident macrophage development and affects neurological function.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteínas / Sistema Nervioso Central / Astrocitos / Microglía / Regulación del Desarrollo de la Expresión Génica / Células Mieloides / Enfermedades del Sistema Nervioso Límite: Animals Idioma: En Revista: Nat Immunol Asunto de la revista: ALERGIA E IMUNOLOGIA Año: 2017 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteínas / Sistema Nervioso Central / Astrocitos / Microglía / Regulación del Desarrollo de la Expresión Génica / Células Mieloides / Enfermedades del Sistema Nervioso Límite: Animals Idioma: En Revista: Nat Immunol Asunto de la revista: ALERGIA E IMUNOLOGIA Año: 2017 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos