{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,4,13]],"date-time":"2025-04-13T01:17:30Z","timestamp":1744507050717},"reference-count":37,"publisher":"Society for Neuroscience","issue":"49","license":[{"start":{"date-parts":[[2009,6,3]],"date-time":"2009-06-03T00:00:00Z","timestamp":1243987200000},"content-version":"vor","delay-in-days":182,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-sa\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Neurosci."],"published-print":{"date-parts":[[2008,12,3]]},"abstract":"<jats:p>The contraction of skeletal muscle is dependent on synaptic transmission through acetylcholine receptors (AChRs) at the neuromuscular junction (NMJ). The lack of an AChR subunit causes a fetal akinesia in humans, leading to death in the first trimester and characteristic features of Fetal Akinesia Deformation Sequences (FADS). A corresponding null mutation of the \u03b4-subunit in zebrafish (<jats:italic>sofa potato; sop<\/jats:italic>) leads to the death of embryos around 5 d postfertilization (dpf). In<jats:italic>sop<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup>mutants, we expressed modified \u03b4-subunits, with one (\u03b41YFP) or two yellow fluorescent protein (\u03b42YFP) molecules fused at the intracellular loop, under the control of an \u03b1-actin promoter. AChRs containing these fusion proteins are fluorescent, assemble on the plasma membrane, make clusters under motor neuron endings, and generate synaptic current. We screened for germ-line transmission of the transgene and established a line of<jats:italic>sop<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup>fish stably expressing the \u03b42YFP. These \u03b42YFP\/<jats:italic>sop<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup>embryos can mount escape behavior close to that of their wild-type siblings. Synaptic currents in these embryos had a smaller amplitude, slower rise time, and slower decay when compared with wild-type fish. Remarkably, these embryos grow to adulthood and display complex behaviors such as feeding and breeding. To the best of our knowledge, this is the first case of a mutant animal corresponding to first trimester lethality in human that has been rescued by a transgene and survived to adulthood. In the rescued fish, a foreign promoter drove the transgene expression and the NMJ had altered synaptic strength. The survival of the transgenic animal delineates requirements for gene therapies of NMJ.<\/jats:p>","DOI":"10.1523\/jneurosci.2814-08.2008","type":"journal-article","created":{"date-parts":[[2008,12,3]],"date-time":"2008-12-03T20:16:24Z","timestamp":1228335384000},"page":"13223-13231","source":"Crossref","is-referenced-by-count":10,"title":["A Modified Acetylcholine Receptor \u03b4-Subunit Enables a Null Mutant to Survive Beyond Sexual Maturation"],"prefix":"10.1523","volume":"28","author":[{"given":"Kimberly E.","family":"Epley","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jason 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