Premium
Astrocytes play an essential role in reversing respiratory disturbances in a mouse model of Rett syndrome
Author(s) -
Bissonnette John,
Lioy Daniel T.,
Hirrlinger Petra G.,
Kirchhoff Frank,
Mandel Gail
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.1064.18
Subject(s) - mecp2 , astrocyte , biology , glial fibrillary acidic protein , rett syndrome , medicine , cre recombinase , endocrinology , microbiology and biotechnology , transgene , immunohistochemistry , genetically modified mouse , gene , immunology , genetics , central nervous system , phenotype
Recent in vitro studies have shown that astrocytes lacking methyl‐CpG‐binding protein 2 (Mecp2) have a non‐cell autonomous effect on neuronal properties such as dendrite arborization and morphology. Here we show that activation of Mecp2 in astrocytes of symptomatic null animals restores a normal breathing pattern. Mice carrying a loxP‐ stop cassette in intron 2 of the Mecp2 gene were crossbred to animals expressing a fusion protein of Cre DNA recombinase and a mutated estrogen receptor under the control of the human glial fibrillary acidic protein (GFAP) promoter. Male offspring are Mecp2 null, but the transcription factor can be restored in astrocytes by tamoxifen injections at any postnatal age. At P45 and older these mice developed apneas (~50/h) and an elevated irregularity score (>0.4). Within 10 days of completing tamoxifen apnea declined, by 3 weeks it reached wild type levels and irregularity improved (~0.25). Immunohistochemistry showed co‐localization of Mecp2 in GFAP‐positive cells in the preBötzinger complex of tamoxifen‐treated mice. The results indicate the important role of astrocyte Mecp2 that functions to control neuronal network activity essential for normal respiration. Support: MOD & IRSF (JB); DFG & EC (FK); HHMI & NIH (GM)