GFAP is necessary for the integrity of CNS white matter architecture and long-term maintenance of myelination.
To investigate the structural role of glial fibrillary acidic protein (GFAP) in vivo, mice carrying a null mutation in GFAP were generated. In 7/14 mutant animals older than 18 months of age, hydrocephalus associated with white matter loss was detected. Mutant mice displayed abnormal myelination including the presence of actively myelinating oligodendrocytes in adults, nonmyelinated axons in optic nerve, and reduced myelin thickness in spinal cord. White matter was poorly vascularized and the blood-brain barrier was structurally and functionally impaired. Astrocytic structure and function were abnormal, consisting of shortened astrocytic cell processes, decreased septation of white matter, and increased CNS extracellular space. Thus, GFAP expression is essential for normal white matter architecture and blood-brain barrier integrity, and its absence leads to late-onset CNS dysmyelination.
Department of Pathology/Division of Neuropathology, Albert Einstein College of Medicine, Bronx, New York 10016, USA.
W
W
Liedtke
W
W
Edelmann
P L
PL
Bieri
F C
FC
Chiu
N J
NJ
Cowan
R
R
Kucherlapati
C S
CS
Raine
D000375:Aging; D000818:Animals; D001755:Blastocyst; D001921:Brain / Q000254:growth & development / Q000473:pathology* / Q000648:ultrastructure; D029742:Caenorhabditis elegans Proteins; D002678:Chimera; D003337:Corpus Callosum / Q000473:pathology; D003433:Crosses, Genetic; D005260:Female; D006580:Genetic Carrier Screening; D005904:Glial Fibrillary Acidic Protein / Q000172:deficiency* / Q000502:physiology*; D008297:Male; D008562:Membrane Glycoproteins / Q000032:analysis; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016253:Microscopy, Immunoelectron; D009900:Optic Nerve / Q000254:growth & development / Q000473:pathology* / Q000648:ultrastructure; D051880:Receptors, Notch; D013116:Spinal Cord / Q000254:growth & development / Q000473:pathology* / Q000648:ultrastructure; D013234:Stem Cells
D029742:Caenorhabditis elegans Proteins; D005904:Glial Fibrillary Acidic Protein; C060620:Glp-1 protein, C elegans; D008562:Membrane Glycoproteins; D051880:Receptors, Notch