title: Conditional disruption of beta 1 integrin in Schwann cells impedes interactions with axons.
abstract: In dystrophic mice, a model of merosin-deficient congenital muscular dystrophy, laminin-2 mutations produce peripheral nerve dysmyelination and render Schwann cells unable to sort bundles of axons. The laminin receptor and the mechanism through which dysmyelination and impaired sorting occur are unknown. We describe mice in which Schwann cell-specific disruption of beta1 integrin, a component of laminin receptors, causes a severe neuropathy with impaired radial sorting of axons. beta 1-null Schwann cells populate nerves, proliferate, and survive normally, but do not extend or maintain normal processes around axons. Interestingly, some Schwann cells surpass this problem to form normal myelin, possibly due to the presence of other laminin receptors such as dystroglycan and alpha 6 beta 4 integrin. These data suggest that beta 1 integrin links laminin in the basal lamina to the cytoskeleton in order for Schwann cells to ensheath axons, and alteration of this linkage contributes to the peripheral neuropathy of congenital muscular dystrophy.
authors.affiliation: Department of Biological and Technological Research, San Raffaele Scientific Institute, 20132 Milan, Italy. feltri.laura@hsr.it
authors.forename: M Laura
authors.initials: ML
authors.lastname: Feltri
authors.forename: Diana
authors.initials: D
authors.lastname: Graus Porta
authors.forename: Stefano C
authors.initials: SC
authors.lastname: Previtali
authors.forename: Alessandro
authors.initials: A
authors.lastname: Nodari
authors.forename: Barbara
authors.initials: B
authors.lastname: Migliavacca
authors.forename: Arianna
authors.initials: A
authors.lastname: Cassetti
authors.forename: Amanda
authors.initials: A
authors.lastname: Littlewood-Evans
authors.forename: Louis F
authors.initials: LF
authors.lastname: Reichardt
authors.forename: Albee
authors.initials: A
authors.lastname: Messing
authors.forename: Angelo
authors.initials: A
authors.lastname: Quattrini
authors.forename: Ulrich
authors.initials: U
authors.lastname: Mueller
authors.forename: Lawrence
authors.initials: L
authors.lastname: Wrabetz
mesh_terms: D000818:Animals; D001369:Axons / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D001973:Bromodeoxyuridine / Q000378:metabolism; D002448:Cell Adhesion; D002455:Cell Division / Q000235:genetics; D048429:Cell Size; D002470:Cell Survival / Q000235:genetics; D004247:DNA / Q000096:biosynthesis; D017353:Gene Deletion; D005786:Gene Expression Regulation; D020287:In Situ Nick-End Labeling; D019012:Integrin beta1 / Q000235:genetics* / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D008818:Mice, Neurologic Mutants; D009137:Muscular Dystrophy, Animal / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D009186:Myelin Sheath / Q000235:genetics / Q000378:metabolism / Q000648:ultrastructure; D009928:Organ Specificity; D017474:Receptors, Laminin / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012583:Schwann Cells / Q000378:metabolism* / Q000473:pathology* / Q000648:ultrastructure
chemical_list: D019012:Integrin beta1; D017474:Receptors, Laminin; D004247:DNA; D001973:Bromodeoxyuridine