{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T13:11:42Z","timestamp":1779196302213,"version":"3.51.4"},"reference-count":43,"publisher":"American Society for Clinical Investigation","issue":"21","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2018,11,2]]},"abstract":"<jats:p>\n                    Glycine encephalopathy (GE), or nonketotic hyperglycinemia (NKH), is a rare recessive genetic disease caused by defective glycine cleavage and characterized by increased accumulation of glycine in all tissues. Here, based on new case reports of\n                    <jats:italic>GLDC<\/jats:italic>\n                    loss-of-function mutations in GE patients, we aimed to generate a zebrafish model of severe GE in order to unravel the molecular mechanism of the disease. Using CRISPR\/Cas9, we knocked out the\n                    <jats:italic>gldc<\/jats:italic>\n                    gene and showed that\n                    <jats:italic>\n                      gldc\n                      <jats:sup>\u2013\/\u2013<\/jats:sup>\n                    <\/jats:italic>\n                    fish recapitulate GE on a molecular level and present a motor phenotype reminiscent of severe GE symptoms. The molecular characterization of\n                    <jats:italic>\n                      gldc\n                      <jats:sup>\u2013\/\u2013<\/jats:sup>\n                    <\/jats:italic>\n                    mutants showed a broad metabolic disturbance affecting amino acids and neurotransmitters other than glycine, with lactic acidosis at stages preceding death. Although a transient imbalance was found in cell proliferation in the brain of\n                    <jats:italic>\n                      gldc\n                      <jats:sup>\u2013\/\u2013<\/jats:sup>\n                    <\/jats:italic>\n                    zebrafish, the main brain networks were not affected, thus suggesting that GE pathogenicity is mainly due to metabolic defects. We confirmed that the\n                    <jats:italic>\n                      gldc\n                      <jats:sup>\u2013\/\u2013<\/jats:sup>\n                    <\/jats:italic>\n                    hypotonic phenotype is due to NMDA and glycine receptor overactivation, and demonstrated that\n                    <jats:italic>gldc<\/jats:italic>\n                    <jats:sup>\u2013\/\u2013<\/jats:sup>\n                    larvae depict exacerbated hyperglycinemia at these synapses. Remarkably, we were able to rescue the motor dysfunction of\n                    <jats:italic>\n                      gldc\n                      <jats:sup>\u2013\/\u2013<\/jats:sup>\n                    <\/jats:italic>\n                    larvae by counterbalancing pharmacologically or genetically the level of glycine at the synapse.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.124642","type":"journal-article","created":{"date-parts":[[2018,10,23]],"date-time":"2018-10-23T17:12:57Z","timestamp":1540314777000},"source":"Crossref","is-referenced-by-count":10,"title":["Glycine decarboxylase deficiency\u2013induced motor dysfunction in zebrafish is rescued by counterbalancing glycine synaptic level"],"prefix":"10.1172","volume":"3","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9123-6232","authenticated-orcid":true,"given":"Rapha\u00eblle","family":"Rich\u00e9","sequence":"first","affiliation":[{"name":"Research Center of the University of Montreal Hospital Center (CRCHUM), Department of Neurosciences, Universit\u00e9 de Montr\u00e9al, Montreal, Quebec, Canada."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Meijiang","family":"Liao","sequence":"additional","affiliation":[{"name":"Research Center of the University of Montreal Hospital Center (CRCHUM), Department of Neurosciences, Universit\u00e9 de Montr\u00e9al, Montreal, Quebec, Canada."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Izabella A.","family":"Pena","sequence":"additional","affiliation":[{"name":"Children\u2019s Hospital of Eastern Ontario Research Institute and Department of Pediatrics, Faculty of Medicine, University of Ottawa, Ontario, Canada."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7868-9616","authenticated-orcid":true,"given":"Kit-Yi","family":"Leung","sequence":"additional","affiliation":[{"name":"Developmental Biology and Cancer Programme, UCL Great Ormond Street Institute of Child Health, University College London, London, United Kingdom."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nathalie","family":"Lepage","sequence":"additional","affiliation":[{"name":"Children\u2019s Hospital of Eastern Ontario Research Institute and Department of Pediatrics, Faculty of Medicine, University of Ottawa, Ontario, Canada."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicolas D.E.","family":"Greene","sequence":"additional","affiliation":[{"name":"Developmental Biology and Cancer Programme, UCL Great Ormond Street Institute of Child Health, University College London, London, United Kingdom."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kyriakie","family":"Sarafoglou","sequence":"additional","affiliation":[{"name":"Division of Pediatric Endocrinology, Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lisa A.","family":"Schimmenti","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology,"},{"name":"Department of Pediatrics, and"},{"name":"Department of Clinical Genomics, Mayo Clinic College of Medicine, Rochester, Minnesota, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pierre","family":"Drapeau","sequence":"additional","affiliation":[{"name":"Research Center of the University of Montreal Hospital Center (CRCHUM), Department of Neurosciences, Universit\u00e9 de Montr\u00e9al, Montreal, Quebec, Canada."},{"name":"DanioDesign Inc., Montr\u00e9al, Quebec, Canada."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"\u00c9ric","family":"Samarut","sequence":"additional","affiliation":[{"name":"Research Center of the University of Montreal Hospital Center (CRCHUM), Department of Neurosciences, Universit\u00e9 de Montr\u00e9al, Montreal, Quebec, Canada."},{"name":"DanioDesign Inc., Montr\u00e9al, Quebec, 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