title: Altered molecular architecture of peripheral nerves in mice lacking the peripheral myelin protein 22 or connexin32.
abstract: Peripheral nerves of mutant mice deficient for peripheral myelin protein 22 (PMP22) or connexin32 (Cx32) display similar pathologies as observed in hereditary human peripheral neuropathies. Mice lacking PMP22 develop focal hypermyelination followed by myelin degeneration and axonal atrophy. Cx32-deficient mice form normal myelin initially but develop demyelination and remyelination at older ages. We have examined the lack of PMP22 or Cx32 on the distribution of other components of the myelin sheath including myelin basic protein (MBP), E-cadherin, and myelin-associated glycoprotein (MAG), as well as the delayed rectifying potassium channel Kv1.1 as an intrinsic membrane protein of axons. In peripheral nerves of wild-type mice, Kv1.1 is present as a pair of juxtaparanodal clusters and a focal line extending longitudinally into the internode, branching parallel and adjacent to Schmidt-Lanterman incisures. Myelinated peripheral nerve fibers of 3-week-old PMP22(0/0) mice show tomacula and abnormally short internodes of variable lengths with minor effects on the localization of E-cadherin and Kv1.1. In older PMP22(0/0) mice, hypomyelinated fibers contain supernumerary Schwann cells and loose focally restricted E-cadherin and Kv1.1 expression. In contrast, remyelinated fibers in adult Cx32(0/0) mice exhibit a correct localization of these marker proteins, except that juxtaparanodal Kv1.1 clusters are aligned in abnormally short intervals of regular distances accompanied by an increased number of Schwann cells. Thus, different degrees of demyelination and remyelination in demyelinating mouse models have variable effects on the confinement of specific proteins to structural and functional internodal domains.
authors.affiliation: Institute of Cell Biology, Swiss Federal Institute of Technology, ETH Hönggerberg, Zürich, Switzerland.
authors.forename: D H
authors.initials: DH
authors.lastname: Neuberg
authors.forename: S
authors.initials: S
authors.lastname: Sancho
authors.forename: U
authors.initials: U
authors.lastname: Suter
mesh_terms: D000818:Animals; D015820:Cadherins / Q000032:analysis; D017630:Connexins / Q000235:genetics*; D005260:Female; D005838:Genotype; D015417:Hereditary Sensory and Motor Neuropathy / Q000503:physiopathology*; D007150:Immunohistochemistry; D051662:Kv1.1 Potassium Channel; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation; D004676:Myelin Basic Protein / Q000032:analysis; D009185:Myelin Proteins / Q000235:genetics*; D009186:Myelin Sheath / Q000737:chemistry* / Q000473:pathology*; D018992:Myelin-Associated Glycoprotein / Q000032:analysis; D010525:Peripheral Nerves / Q000737:chemistry* / Q000473:pathology*; D015221:Potassium Channels / Q000032:analysis; D024642:Potassium Channels, Voltage-Gated; D013997:Time Factors; D000097002:Gap Junction beta-1 Protein
chemical_list: D015820:Cadherins; D017630:Connexins; D051662:Kv1.1 Potassium Channel; D004676:Myelin Basic Protein; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D000097002:Gap Junction beta-1 Protein; C496947:Kcna1 protein, mouse; C489545:Pmp22 protein, mouse