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Nuclear receptor interaction protein interacts with CaM to activate calcineurin and CaMKII signalling. The conventional NRIP knockout mice (global knockout) showed muscular abnormality with reduction of muscle oxidative functions and motor function defects.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>To investigate the role of NRIP on neuromuscular system, we generated muscle\u2010restricted NRIP knockout mice [conditional knockout (cKO)]. The muscle functions (including oxidative muscle markers and muscle strength) and lumbar motor neuron functions [motor neuron number, axon denervation, neuromuscular junction (NMJ)] were tested. The laser\u2010captured microdissection at NMJ of skeletal muscles and adenovirus gene therapy for rescued effects were performed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The cKO mice showed muscular abnormality with reduction of muscle oxidative functions and impaired motor performances as global knockout mice. To our surprise, cKO mice also displayed motor neuron degeneration with abnormal architecture of NMJ. Specifically, the cKO mice revealed reduced motor neuron number with small neuronal size in lumbar spinal cord as well as denervating change, small motor endplates, and decreased myonuclei number at NMJ in skeletal muscles. To explore the mechanisms, we screened various muscle\u2010derived factors and found that myogenin is a potential candidate that myogenin expression was lower in skeletal muscles of cKO mice than wild\u2010type mice. Because NRIP and myogenin were colocalized around acetylcholine receptors at NMJ, we extracted RNA from synaptic and extrasynaptic regions of muscles using laser capture microdissection and showed that myogenin expression was especially lower at synaptic region in cKO than wild\u2010type mice. Notably, overexpression of myogenin using intramuscular adenovirus encoding myogenin treatment rescued abnormal NMJ architecture and preserved motor neuron death in cKO mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>In summary, we demonstrated that deprivation of NRIP decreases myogenin expression at NMJ, possibly leading to abnormal NMJ formation, denervation of acetylcholine receptor, and subsequent loss of spinal motor neuron. Overexpression of myogenin in cKO mice can partially rescue abnormal NMJ architecture and motor neuron death. Therefore, muscular NRIP is a novel trophic factor supporting spinal motor neuron via stabilization of NMJ by myogenin expression.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jcsm.12299","type":"journal-article","created":{"date-parts":[[2018,4,2]],"date-time":"2018-04-02T12:24:40Z","timestamp":1522671880000},"page":"771-785","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Muscle\u2010restricted nuclear receptor interaction protein knockout causes motor neuron degeneration through down\u2010regulation of myogenin at the neuromuscular junction"],"prefix":"10.1002","volume":"9","author":[{"given":"Hsin\u2010Hsiung","family":"Chen","sequence":"first","affiliation":[{"name":"Graduate Institute of Microbiology, College of Medicine National Taiwan University  7F, No. 1, Sec. 1, Jen\u2010Ai Rd. 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Taipei 100 Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pei\u2010Yu","family":"Wang","sequence":"additional","affiliation":[{"name":"Graduate Institute of Brain and Mind Sciences, College of Medicine National Taiwan University  Taipei Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yeou\u2010Ping","family":"Tsao","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology Mackay Memorial Hospital  Taipei Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Show\u2010Li","family":"Chen","sequence":"additional","affiliation":[{"name":"Graduate Institute of Microbiology, College of Medicine National Taiwan University  7F, No. 1, Sec. 1, Jen\u2010Ai Rd. 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