title: Spontaneous optic nerve compression in the osteopetrotic (op/op) mouse: a novel model of myelination failure.
abstract: We report a focal disturbance in myelination of the optic nerve in the osteopetrotic (op/op) mouse, which results from a spontaneous compression of the nerve resulting from stenosis of the optic canal. The growth of the op/op optic nerve was significantly affected, being maximally suppressed at postnatal day 30 (P30; 33% of age matched control). Myelination of the nerve in the optic canal was significantly delayed at P15, and myelin was almost completely absent at P30. The size of nerves and myelination were conserved both in the intracranial and intraorbital segments at P30, suggesting that the axons in the compressed site are spared in all animals at P30. Interestingly, we observed recovery both in the nerve size and the density of myelinated axons at 7 months in almost half of the optic nerves examined, although some nerves lost axons and became atrophic. In vivo and ex vivo electrophysiological examinations of P30 op/op mice showed that nerve conduction was significantly delayed but not blocked with partial recovery in some mice by 7 months. Transcardial perfusion of FITC-labeled albumin suggested that local ischemia was at least in part the cause of this myelination failure. These results suggest that the primary abnormality is dysmyelination of the optic nerve in early development. This noninvasive model system will be a valuable tool to study the effects of nerve compression on the function and survival of oligodendrocyte progenitor cells/oligodendrocytes and axons and to explore the mechanism of redistribution of oligodendrocyte progenitor cells with compensatory myelination.
authors: Department of Medical Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, Wisconsin 53706, USA.
authors: Yoichi
authors: Y
authors: Kondo
authors: Jenna M
authors: JM
authors: Ramaker
authors: Abigail B
authors: AB
authors: Radcliff
authors: Simona
authors: S
authors: Baldassari
authors: Joshua A
authors: JA
authors: Mayer
authors: James N
authors: JN
authors: Ver Hoeve
authors: Chuan-Li
authors: CL
authors: Zhang
authors: Shing-Yan
authors: SY
authors: Chiu
authors: Raymond J
authors: RJ
authors: Colello
authors: Ian D
authors: ID
authors: Duncan
mesh_terms: D000818:Animals; D003711:Demyelinating Diseases / Q000235:genetics* / Q000473:pathology*; D004195:Disease Models, Animal; D051379:Mice; D008818:Mice, Neurologic Mutants; D009408:Nerve Compression Syndromes / Q000235:genetics / Q000473:pathology*; D009413:Nerve Fibers, Myelinated / Q000473:pathology / Q000502:physiology; D009431:Neural Conduction / Q000235:genetics; D009836:Oligodendroglia / Q000473:pathology / Q000502:physiology; D009900:Optic Nerve / Q000473:pathology* / Q000502:physiology; D009901:Optic Nerve Diseases / Q000235:genetics* / Q000473:pathology*; D010022:Osteopetrosis / Q000235:genetics; D013234:Stem Cells / Q000473:pathology / Q000502:physiology