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Distribution of phosphorylated glial fibrillary acidic protein in the mouse central nervous system
Author(s) -
Takemura Masaaki,
Nishiyama Hiroshi,
Itohara Shigeyoshi
Publication year - 2002
Publication title -
genes to cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.912
H-Index - 115
eISSN - 1365-2443
pISSN - 1356-9597
DOI - 10.1046/j.1365-2443.2002.00513.x
Subject(s) - glial fibrillary acidic protein , gfap stain , biology , astrocyte , central nervous system , microbiology and biotechnology , phosphorylation , pathology , neuroscience , immunohistochemistry , immunology , medicine
Background: Glial fibrillary acidic protein (GFAP) is the principal component of intermediate filaments (IFs) in mature astrocytes in the central nervous system (CNS). Like other IF proteins, GFAP has multiple phosphorylation sites in the N‐terminal head domain. The distribution of phospho‐GFAP in vivo has not been elucidated. Results: We generated Gfap hwt knock‐in mice, in which the coding region for the head domain of GFAP is replaced with the corresponding human sequence. In combination with a series of monoclonal antibodies (mAbs) reactive to human phospho‐GFAP, we visualized the distribution of phospho‐GFAP in vivo in mice. GFAP phosphorylated at Thr7, Ser8 and/or Ser13 increased postnatally in the CNS of these mice. Limited populations of GFAP‐positive astrocytes were labelled with anti‐phospho‐GFAP mAbs in most brain areas, whereas almost all the astrocytes in the optic nerve and spinal cord were labelled. Astrocytes in the subventricular zone and rostral migratory stream preferentially contained phospho‐GFAP. In a cold injury model of the cerebral cortex, we detected phospho‐GFAP in reactive astrocytes at 2–3 weeks after the injury. Conclusions: Phospho‐GFAP provides a molecular marker indicating the heterogeneity of astrocytes, and Gfap hwt knock‐in mice will aid in monitoring intracellular conditions of astrocytes, under various conditions. Our results suggest that the phosphorylation of GFAP plays a role in non‐dividing astrocytes in vivo.