title: Dependence of paranodal junctional gap width on transverse bands.
abstract: Mouse mutants with paranodal junctional (PNJ) defects display variable degrees of neurological impairment. In this study we compare control paranodes with those from three mouse mutants that differ with respect to a conspicuous PNJ component, the transverse bands (TBs). We hypothesize that TBs link the apposed junctional membranes together at a fixed distance and thereby determine the width of the junctional gap, which may in turn determine the extent to which nodal action currents can be short-circuited underneath the myelin sheath. Electron micrographs of aldehyde-fixed control PNJs, in which TBs are abundant, show a consistent junctional gap of ∼3.5 nm. In Caspr-null PNJs, which lack TBs entirely, the gap is wider (∼6-7 nm) and more variable. In CST-null PNJs, which have only occasional TBs, the mean PNJ gap width is comparable to that in Caspr-null mice. In the shaking mutant, in contrast, which has approximately 60% of the normal complement of TBs, mean PNJ gap width is not significantly different from that in controls. Correspondingly, shaking mice are much less impaired neurologically than either Caspr-null or CST-null mice. We conclude that in the absence or gross diminution of TBs, mean PNJ gap width increases significantly and suggest that this difference could underlie some of the neurological impairment seen in those mutants. Surprisingly, even in the absence of TBs, paranodes are to some extent maintained in their usual form, implying that in addition to TBs, other factors govern the formation and maintenance of overall paranodal structure.
authors.affiliation: Department of Physiology & Neuroscience, New York University School of Medicine, New York, New York 10016, USA. rosenj03@med.nyu.edu
authors.forename: Jack
authors.initials: J
authors.lastname: Rosenbluth
authors.forename: Chris
authors.initials: C
authors.lastname: Petzold
authors.forename: Elior
authors.initials: E
authors.lastname: Peles
mesh_terms: D000818:Animals; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics; D003711:Demyelinating Diseases / Q000473:pathology; D005260:Female; D017629:Gap Junctions / Q000737:chemistry / Q000473:pathology / Q000502:physiology*; D007365:Intercellular Junctions / Q000737:chemistry / Q000473:pathology / Q000502:physiology*; D008297:Male; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008818:Mice, Neurologic Mutants; D009103:Multiple Sclerosis / Q000473:pathology; D009186:Myelin Sheath / Q000473:pathology; D009441:Neurilemma / Q000473:pathology; D011901:Ranvier's Nodes / Q000473:pathology / Q000502:physiology
chemical_list: D015816:Cell Adhesion Molecules, Neuronal; C491322:Cntnap1 protein, mouse