title: Postsynaptic abnormalities at the neuromuscular junctions of utrophin-deficient mice.
abstract: Utrophin is a dystrophin-related cytoskeletal protein expressed in many tissues. It is thought to link F-actin in the internal cytoskeleton to a transmembrane protein complex similar to the dystrophin protein complex (DPC). At the adult neuromuscular junction (NMJ), utrophin is precisely colocalized with acetylcholine receptors (AChRs) and recent studies have suggested a role for utrophin in AChR cluster formation or maintenance during NMJ differentiation. We have disrupted utrophin expression by gene targeting in the mouse. Such mice have no utrophin detectable by Western blotting or immunocytochemistry. Utrophin-deficient mice are healthy and show no signs of weakness. However, their NMJs have reduced numbers of AChRs (alpha-bungarotoxin [alpha-BgTx] binding reduced to approximately 60% normal) and decreased postsynaptic folding, though only minimal electrophysiological changes. Utrophin is thus not essential for AChR clustering at the NMJ but may act as a component of the postsynaptic cytoskeleton, contributing to the development or maintenance of the postsynaptic folds. Defects of utrophin could underlie some forms of congenital myasthenic syndrome in which a reduction of postsynaptic folds is observed.
authors.affiliation: Department of Biochemistry, University of Oxford, United Kingdom.
authors.forename: A E
authors.initials: AE
authors.lastname: Deconinck
authors.forename: A C
authors.initials: AC
authors.lastname: Potter
authors.forename: J M
authors.initials: JM
authors.lastname: Tinsley
authors.forename: S J
authors.initials: SJ
authors.lastname: Wood
authors.forename: R
authors.initials: R
authors.lastname: Vater
authors.forename: C
authors.initials: C
authors.lastname: Young
authors.forename: L
authors.initials: L
authors.lastname: Metzinger
authors.forename: A
authors.initials: A
authors.lastname: Vincent
authors.forename: C R
authors.initials: CR
authors.lastname: Slater
authors.forename: K E
authors.initials: KE
authors.lastname: Davies
mesh_terms: D000818:Animals; D015153:Blotting, Western; D003598:Cytoskeletal Proteins / Q000172:deficiency* / Q000235:genetics*; D005260:Female; D007150:Immunohistochemistry; D008297:Male; D008565:Membrane Proteins / Q000172:deficiency* / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008813:Mice, Inbred ICR; D018345:Mice, Knockout; D018482:Muscle, Skeletal / Q000737:chemistry / Q000276:immunology; D009469:Neuromuscular Junction / Q000737:chemistry / Q000378:metabolism / Q000503:physiopathology*; D010641:Phenotype; D011950:Receptors, Cholinergic / Q000378:metabolism; D013569:Synapses / Q000473:pathology*; D009435:Synaptic Transmission; D049411:Utrophin
chemical_list: D003598:Cytoskeletal Proteins; D008565:Membrane Proteins; D011950:Receptors, Cholinergic; C483600:Utrn protein, mouse; D049411:Utrophin