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In this study, NGLY1\u2010deficient, patient\u2010derived induced pluripotent stem cells (iPSCs) are differentiated into motoneurons (MNs) to identify disease phenotypes analogous to clinical disease pathology with significant deficits apparent in the NGLY1\u2010deficient lines compared to the control. A neuromuscular junction (NMJ) model is developed using patient and wild type MNs to study functional differences between healthy and diseased NMJs. Reduced axon length, increased and shortened axon branches, MN action potential (AP) bursting, and decreased AP firing rate and amplitude are observed in the NGLY1\u2010deficient MNs in monoculture. When transitioned to the NMJ\u2010coculture system, deficits in NMJ number, stability, failure rate, and synchronicity with indirect skeletal muscle stimulation are observed. This project establishes a phenotypic NGLY1 model for investigation of possible therapeutics and investigations into mechanistic deficits in the system.<\/jats:p>","DOI":"10.1002\/adtp.202200009","type":"journal-article","created":{"date-parts":[[2022,7,15]],"date-time":"2022-07-15T03:21:37Z","timestamp":1657855297000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["An Induced Pluripotent Stem Cell\u2010Derived Neuromuscular Junction Platform for Study of the NGLY1\u2010Congenital Disorder of Deglycosylation"],"prefix":"10.1002","volume":"5","author":[{"given":"Trevor","family":"Sasserath","sequence":"first","affiliation":[{"name":"Hesperos, Inc.  12501 Research Parkway, Suite 100 Orlando FL 32826 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ashley L.","family":"Robertson","sequence":"additional","affiliation":[{"name":"Hesperos, Inc.  12501 Research Parkway, Suite 100 Orlando FL 32826 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roxana","family":"Mendez","sequence":"additional","affiliation":[{"name":"NanoScience Technology Center University of Central Florida  12424 Research Parkway, Suite 400 Orlando FL 32826 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tristan T.","family":"Hays","sequence":"additional","affiliation":[{"name":"Hesperos, Inc.  12501 Research Parkway, Suite 100 Orlando FL 32826 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ethan","family":"Smith","sequence":"additional","affiliation":[{"name":"Hesperos, Inc.  12501 Research Parkway, Suite 100 Orlando FL 32826 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Helena","family":"Cooper","sequence":"additional","affiliation":[{"name":"Hesperos, Inc.  12501 Research Parkway, Suite 100 Orlando FL 32826 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nesar","family":"Akanda","sequence":"additional","affiliation":[{"name":"NanoScience Technology Center University of Central Florida  12424 Research Parkway, Suite 400 Orlando FL 32826 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John W.","family":"Rumsey","sequence":"additional","affiliation":[{"name":"Hesperos, Inc.  12501 Research Parkway, Suite 100 Orlando FL 32826 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiufang","family":"Guo","sequence":"additional","affiliation":[{"name":"NanoScience Technology Center University of Central Florida  12424 Research Parkway, Suite 400 Orlando FL 32826 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Atena","family":"Farkhondeh","sequence":"additional","affiliation":[{"name":"National Center for Advancing Translational Sciences National Institutes of Health  9800 Medical Center Drive, Building C, Room 310W Rockville MD 20850 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manisha","family":"Pradhan","sequence":"additional","affiliation":[{"name":"National Center for Advancing Translational Sciences National Institutes of Health  9800 Medical Center Drive, Building C, Room 310W Rockville MD 20850 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karsten","family":"Baumgaertel","sequence":"additional","affiliation":[{"name":"Travere Therapeutics  3611 Valley Centre Drive, Suite 300 San Diego CA 92130 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthew","family":"Might","sequence":"additional","affiliation":[{"name":"Hugh Kaul Precision Medicine Institute University of Alabama at Birmingham  510 20th St S, Office 858B Birmingham AL 35210 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Steven","family":"Rodems","sequence":"additional","affiliation":[{"name":"Travere Therapeutics  3611 Valley Centre Drive, Suite 300 San Diego CA 92130 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Zheng","sequence":"additional","affiliation":[{"name":"National Center for Advancing Translational Sciences National Institutes of Health  9800 Medical Center Drive, Building C, Room 310W Rockville MD 20850 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1621-3006","authenticated-orcid":false,"given":"James J.","family":"Hickman","sequence":"additional","affiliation":[{"name":"Hesperos, Inc.  12501 Research Parkway, Suite 100 Orlando FL 32826 USA"},{"name":"NanoScience Technology Center University of Central Florida  12424 Research Parkway, Suite 400 Orlando FL 32826 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2022,8,19]]},"reference":[{"key":"e_1_2_9_1_1","unstructured":"a)A.Omar K.Marwaha P. 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