{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T17:10:27Z","timestamp":1774977027817,"version":"3.50.1"},"reference-count":72,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2023,1,30]],"date-time":"2023-01-30T00:00:00Z","timestamp":1675036800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["R21NS120079\u201001"],"award-info":[{"award-number":["R21NS120079\u201001"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Genes Brain and Behavior"],"published-print":{"date-parts":[[2023,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    CHARGE syndrome is a heterogeneous disorder characterized by a spectrum of defects affecting multiple tissues and behavioral difficulties such as autism, attention\u2010deficit\/hyperactivity disorder, obsessive\u2013compulsive disorder, anxiety, and sensory deficits. Most CHARGE cases arise from\n                    <jats:italic>de novo<\/jats:italic>\n                    , loss\u2010of\u2010function mutations in chromodomain\u2010helicase\u2010DNA\u2010binding\u2010protein\u20107 (CHD7). CHD7 is required for processes such as neuronal differentiation and neural crest cell migration, but how CHD7 affects neural circuit function to regulate behavior is unclear. To investigate the pathophysiology of behavioral symptoms in CHARGE, we established a mutant\n                    <jats:italic>chd7<\/jats:italic>\n                    zebrafish line that recapitulates multiple CHARGE phenotypes including ear, cardiac, and craniofacial defects. Using a panel of behavioral assays, we found that\n                    <jats:italic>chd7<\/jats:italic>\n                    mutants have specific auditory and visual behavior deficits that are independent of defects in sensory structures. Mauthner cell\u2010dependent short\u2010latency acoustic startle responses are normal in\n                    <jats:italic>chd7<\/jats:italic>\n                    mutants, while Mauthner\u2010independent long\u2010latency responses are reduced. Responses to sudden decreases in light are also reduced in mutants, while responses to sudden increases in light are normal, suggesting that the retinal OFF pathway may be affected. Furthermore, by analyzing multiple\n                    <jats:italic>chd7<\/jats:italic>\n                    alleles we observed that the penetrance of morphological and behavioral phenotypes is influenced by genetic background but that it also depends on the mutation location, with a chromodomain mutation causing the highest penetrance. This pattern is consistent with analysis of a CHARGE patient dataset in which symptom penetrance was highest in subjects with mutations in the CHD7 chromodomains. These results provide new insight into the heterogeneity of CHARGE and will inform future work to define CHD7\u2010dependent neurobehavioral mechanisms.\n                  <\/jats:p>","DOI":"10.1111\/gbb.12839","type":"journal-article","created":{"date-parts":[[2023,1,30]],"date-time":"2023-01-30T19:25:40Z","timestamp":1675106740000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Morphological and sensorimotor phenotypes in a zebrafish\n                    <scp>CHARGE<\/scp>\n                    syndrome model are domain\u2010dependent"],"prefix":"10.1111","volume":"22","author":[{"given":"Dana R.","family":"Hodorovich","sequence":"first","affiliation":[{"name":"Department of Biological Sciences North Carolina State University  Raleigh North Carolina USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patrick M.","family":"Lindsley","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences North Carolina State University  Raleigh North Carolina USA"},{"name":"University of Virginia School of Medicine, University of Virginia  Charlottesville VA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Austen A.","family":"Berry","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences North Carolina State University  Raleigh North Carolina USA"},{"name":"Biogen  Durham NC USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Derek F.","family":"Burton","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences North Carolina State University  Raleigh North Carolina USA"},{"name":"Washington University  St. Louis MO USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8087-6181","authenticated-orcid":false,"given":"Kurt C.","family":"Marsden","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences North 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