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A transgenic mouse model of the slow‐channel syndrome
Author(s) -
Gomez Christopher M.,
Bhattacharyya Bula B.,
Charnet Pierre,
Day John W.,
Labarca Cesar,
Wollmann Robert L.,
Lambert Edward H.
Publication year - 1996
Publication title -
muscle and nerve
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.025
H-Index - 145
eISSN - 1097-4598
pISSN - 0148-639X
DOI - 10.1002/(sici)1097-4598(199601)19:1<79::aid-mus11>3.0.co;2-z
Subject(s) - acetylcholine receptor , curare , neuromuscular transmission , neuromuscular junction , genetically modified mouse , electrophysiology , transgene , neuroscience , neurotransmission , acetylcholine , in vivo , mutation , congenital myasthenic syndrome , chemistry , biology , biophysics , microbiology and biotechnology , endocrinology , receptor , genetics , gene
To investigate the effect of acetylcholine receptor (AChR) mutations on neuromuscular transmission and to develop a model for the human neuromuscular disease, the slow‐channel syndrome, we generated transgenic mice with abnormal AChRs using a δ subunit with a mutation in the ion channel domain. In three transgenic lines, nerve‐evoked end‐plate currents and spontaneous miniature end‐plate currents (MEPCs) had prolonged decay phases and MEPC amplitudes were reduced by 33%. Single nerve stimuli elicited repetitive compound muscle action potentials in vivo. Transgenic mice were abnormally sensitive to the neuromuscular blocker, curare. These observations demonstrate that we can predictably alter AChR function, synaptic responses, and muscle fiber excitation in vivo by overexpressing subunits containing well‐defined mutations. Furthermore, these data support the hypothesis that the electrophysiological findings in the neuromuscular disorder, the slow‐channel syndrome, are due to mutant AChRs. © 1996 John Wiley & Sons, Inc.