Zebrafish model for congenital myasthenic syndrome reveals mechanisms causal to developmental recovery

Michael Walogorsky, Rebecca Mongeon, Hua Wen, Nathan R. Nelson, Jason M. Urban, Fumihito Ono, Gail Mandel, Paul Brehm

Research output: Contribution to journalArticle

10 Scopus citations

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 ofmuscle function. The zebrafish mutant line, twister, models SCS in terms of a dominant mutation in the α subunit (αtwi) 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 αtwiβδγ 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 αtwi mutation. Thus, the continued expression of αtwi 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.

Original languageEnglish (US)
Pages (from-to)17711-17716
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume109
Issue number43
DOIs
StatePublished - Oct 23 2012

Keywords

  • Neuromuscular
  • Nicotinic receptor
  • Quinidine

ASJC Scopus subject areas

  • General

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