PUBLICATION

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

Authors
Walogorsky, M., Mongeon, R., Wen, H., Nelson, N.R., Urban, J.M., Ono, F., Mandel, G., and Brehm, P.
ID
ZDB-PUB-121016-22
Date
2012
Source
Proceedings of the National Academy of Sciences of the United States of America   109(43): 17711-17716 (Journal)
Registered Authors
Ono, Fumihito, Urban, Jason
Keywords
neuromuscular, quinidine, nicotinic receptor
MeSH Terms
  • Animals
  • Base Sequence
  • DNA Primers
  • Disease Models, Animal*
  • Myasthenic Syndromes, Congenital/etiology*
  • Myasthenic Syndromes, Congenital/physiopathology
  • Patch-Clamp Techniques
  • Zebrafish
PubMed
23045675 Full text @ Proc. Natl. Acad. Sci. USA
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 (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 γε switch.

Genes / Markers
Figures
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping