title: Zebrafish model for congenital myasthenic syndrome reveals mechanisms causal to developmental recovery.
abstract: Mutations in muscle ACh receptors cause slow-channel syndrome (SCS) and Escobar syndrome, two forms of congenital myasthenia. SCS is a dominant disorder with mutations reported for all receptor subunits except γ. Escobar syndrome is distinct, with mutations located exclusively in γ, and characterized by developmental improvement of muscle function. The zebrafish mutant line, twister, models SCS in terms of a dominant mutation in the α subunit (α(twi)) but shows the behavioral improvement associated with Escobar syndrome. Here, we present a unique electrophysiological study into developmental improvement for a myasthenic syndrome. The embryonic α(twi)βδγ receptor isoform produces slowly decaying synaptic currents typical of SCS that transit to a much faster decay upon the appearance of adult ε, despite the α(twi) mutation. Thus, the continued expression of α(twi) into adulthood is tolerated because of the ε expression and associated recovery, raising the likelihood of unappreciated myasthenic cases that benefit from the γ-ε switch.
authors.affiliation: Vollum Institute, Oregon Health and Science University, Portland, OR 97239, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Walogorsky
authors.forename: Rebecca
authors.initials: R
authors.lastname: Mongeon
authors.forename: Hua
authors.initials: H
authors.lastname: Wen
authors.forename: Nathan R
authors.initials: NR
authors.lastname: Nelson
authors.forename: Jason M
authors.initials: JM
authors.lastname: Urban
authors.forename: Fumihito
authors.initials: F
authors.lastname: Ono
authors.forename: Gail
authors.initials: G
authors.lastname: Mandel
authors.forename: Paul
authors.initials: P
authors.lastname: Brehm
mesh_terms: D000818:Animals; D001483:Base Sequence; D017931:DNA Primers; D004195:Disease Models, Animal; D020294:Myasthenic Syndromes, Congenital / Q000209:etiology* / Q000503:physiopathology; D018408:Patch-Clamp Techniques; D015027:Zebrafish
chemical_list: D017931:DNA Primers