Technical report: exploring the basis of congenital myasthenic syndromes in an undergraduate course, using the model organism, Caenorhabditis elegans.
Mutations affecting acetylcholine receptors have been causally linked to the development of congenital myasthenic syndromes (CMS) in humans resulting from neuromuscular transmission defects. In an undergraduate Molecular Neurobiology course, the molecular basis of CMS was explored through study of a Caenorhabditis elegans model of the disease. The nicotinic acetylcholine receptor (nAChR), located on the postsynaptic muscle cell membrane, contains a pentameric ring structure comprised of five homologous subunits. In the nematode C. elegans, unc-63 encodes an α subunit of nAChR. UNC-63 is required for the function of nAChR at the neuromuscular junction. Mutations in unc-63 result in defects in locomotion and egg-laying and may be used as models for CMS. Here, we describe the responses of four unc-63 mutants to the cholinesterase inhibitor pyridostigmine bromide (range 0.9-15.6 mM in this study), a treatment for CMS that mitigates deficiencies in cholinergic transmission by elevating synaptic ACh levels. Our results show that 15.6 mM pyridostigmine bromide enhanced mobility in two alleles, depressed mobility in one allele and in N2, while having no effect on the fourth allele. This indicates that while pyridostigmine bromide may be effective at ameliorating symptoms of CMS in certain cases, it may not be a suitable treatment for all individuals due to the diverse etiology of this disease. Students in the Molecular Neurobiology course enhanced their experience in scientific research by conducting an experiment designed to increase understanding of genetic defects of neurological function.
Kaas
Bonnie
B
The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Vaidya
Avinash R
AR
Leatherman
Amanda
A
Schleidt
Stephanie
S
Kohn
Rebecca Eustance
RE
D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics* / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000235:genetics* / Q000378:metabolism; D002800:Cholinesterase Inhibitors / Q000494:pharmacology; D004195:Disease Models, Animal; D004504:Education, Medical, Undergraduate / Q000379:methods*; D009154:Mutation; D020294:Myasthenic Syndromes, Congenital / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D011729:Pyridostigmine Bromide / Q000494:pharmacology; D011978:Receptors, Nicotinic / Q000235:genetics* / Q000378:metabolism
D029742:Caenorhabditis elegans Proteins; D002800:Cholinesterase Inhibitors; D011978:Receptors, Nicotinic; C493164:Unc-63 protein, C elegans; D011729:Pyridostigmine Bromide