title: Deletion of oligodendrocyte Cx32 and astrocyte Cx43 causes white matter vacuolation, astrocyte loss and early mortality.
abstract: CNS glia exhibit a variety of gap junctional interactions: between neighboring astrocytes, between neighboring oligodendrocytes, between astrocytes and oligodendrocytes, and as 'reflexive' structures between layers of myelin in oligodendrocytes. Together, these junctions are thought to form a network facilitating absorption and removal of extracellular K(+) released during neuronal activity. In mice, loss of the two major oligodendrocyte connexins causes severe demyelination and early mortality, while loss of the two major astrocyte connexins causes mild dysmyelination and sensorimotor impairment, suggesting that reflexive and/or oligo-oligo coupling may be more important for the maintenance of myelin than other forms. To further explore the functional relationships between glial connexins, we generated double knockout mice lacking one oligodendrocyte and one astrocyte connexin. Cx32-Cx43 dKO animals develop white matter vacuolation without obvious ultrastructural abnormalities in myelin. Progressive loss of astrocytes but not oligodendrocytes or microglia accompanies sensorimotor impairment, seizure activity and early mortality at around 16 weeks of age. Our data reveal an unexpected role for connexins in the survival of white matter astrocytes, requiring the expression of particular isoforms in both oligodendrocytes and astrocytes.
authors.affiliation: Department of Neurobiology, Harvard Medical School, 220 Longwood Ave., Boston, Massachusetts 02115, USA.
authors.forename: Laura M
authors.initials: LM
authors.lastname: Magnotti
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Goodenough
authors.forename: David L
authors.initials: DL
authors.lastname: Paul
mesh_terms: D000367:Age Factors; D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D016923:Cell Death; D018031:Connexin 43 / Q000172:deficiency*; D017630:Connexins / Q000172:deficiency*; D018450:Disease Progression; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics; D006801:Humans; D056784:Leukoencephalopathies / Q000150:complications / Q000235:genetics / Q000401:mortality; D051379:Mice; D008822:Mice, Transgenic; D046529:Microscopy, Electron, Transmission; D009069:Movement Disorders / Q000209:etiology / Q000235:genetics / Q000473:pathology; D009186:Myelin Sheath / Q000473:pathology / Q000648:ultrastructure; D009413:Nerve Fibers, Myelinated / Q000473:pathology* / Q000648:ultrastructure; D009836:Oligodendroglia / Q000378:metabolism*; D012640:Seizures / Q000209:etiology / Q000235:genetics / Q000473:pathology; D000097002:Gap Junction beta-1 Protein
chemical_list: D018031:Connexin 43; D017630:Connexins; D005904:Glial Fibrillary Acidic Protein; D000097002:Gap Junction beta-1 Protein