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Caveolin‐1's role on the neuromuscular junction of αC418W SCCMS mice
Author(s) -
Yan June Kalay,
Reyes Jose Gabriel Grajales,
Quesada Orestes,
Dominicci Jose Lasalde
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.lb831
Subject(s) - acetylcholine receptor , neuromuscular junction , neuromuscular transmission , nicotinic agonist , nicotinic acetylcholine receptor , neuroscience , biology , congenital myasthenic syndrome , transgene , microbiology and biotechnology , acetylcholine , caveolin 3 , genetically modified mouse , small hairpin rna , colocalization , neurotransmission , receptor , genetics , endocrinology , gene , gene knockdown , signal transduction , caveolae
Slow Channel Congenital Myasthenic Syndrome (SCCMS) is an inherited genetic disorder caused by mutations in the muscle nicotinic acetylcholine receptors (nAChRs) affecting the neuromuscular transmission. Despite the extensive research performed, this disease still challenges many patients by causing muscle weakness, fatigue, and even death in severe cases. To further characterize this disease, we used transgenic mice models to study the role of caveolin‐1 protein and its relationship with nAChRs expressing the αC418W, a SCCMS‐causing mutation. This mutation shows a caveolin‐1 binding motif that arrests the nAChR in lipid rafts. To study this relationship, we silenced the expression of caveolin‐1 in the muscle endplate by RNA interference and performed immunohistochemistry experiments on the Tibialis anterior (TA) muscle to observe the colocalization of caveolin‐1 and the acetylcholine receptors. We were able to knock down the expression of caveolin‐1 by transfecting the TA muscle with three different shRNA clones through electroporation, clone 2 being the most efficient. These results would allow us to determine the role of caveolin‐1 in the synaptic transmission of transgenic mice expressing the αC418W mutation through electrophysiological studies. Ultimately, this would provide us with better understanding of this rare neurodegenerative disease in efforts of improving current treatments and elucidating new approaches. Work supported by “URM: Mentoring Program in Neural Circuits and Behavior at the University of Puerto Rico”, Award No. DBI‐0932955.