| First Author | Chevessier F | Year | 2008 |
| Journal | Hum Mol Genet | Volume | 17 |
| Issue | 22 | Pages | 3577-95 |
| PubMed ID | 18718936 | Mgi Jnum | J:141024 |
| Mgi Id | MGI:3815258 | Doi | 10.1093/hmg/ddn251 |
| Citation | Chevessier F, et al. (2008) A mouse model for congenital myasthenic syndrome due to MuSK mutations reveals defects in structure and function of neuromuscular junctions. Hum Mol Genet 17(22):3577-95 |
| abstractText | In the muscle-specific tyrosine kinase receptor gene MUSK, a heteroallelic missense and a null mutation were identified in a patient suffering from a congenital myasthenic syndrome (CMS). We generated one mouse line carrying the homozygous missense mutation V789M in musk (musk(V789M/V789M) mice) and a second hemizygous line, resembling the patient genotype, with the V789M mutation on one allele and an allele lacking the kinase domain (musk(V789M/-) mice). We report here that musk(V789M/V789M) mice present no obvious abnormal phenotype regarding weight, muscle function and viability. In contrast, adult musk(V789M/-) mice suffer from severe muscle weakness, exhibit shrinkage of pelvic and scapular regions and hunchback. Musk(V789M/-) diaphragm develops less force upon direct or nerve-induced stimulation. A profound tetanic fade is observed following nerve-evoked muscle contraction, and fatigue resistance is severely impaired upon a train of tetanic nerve stimulations. Electrophysiological measurements indicate that fatigable muscle weakness is due to impaired neurotransmission as observed in a patient suffering from a CMS. The diaphragm of adult musk(V789M/-) mice exhibits pronounced changes in endplate architecture, distribution and innervation pattern. Thus, the missense mutation V789M in MuSK acts as a hypomorphic mutation and leads to insufficiency in MuSK function in musk(V789M/-) mutants. These mutant mice represent valuable models for elucidating the roles of MuSK for synapse formation, maturation and maintenance as well as for studying the pathophysiology of a CMS due to MuSK mutations. |
