{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T13:05:30Z","timestamp":1783602330692,"version":"3.55.0"},"reference-count":46,"publisher":"The Company of Biologists","issue":"3","license":[{"start":{"date-parts":[[2022,3,8]],"date-time":"2022-03-08T00:00:00Z","timestamp":1646697600000},"content-version":"vor","delay-in-days":7,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100000923","name":"Australian Research Council","doi-asserted-by":"crossref","award":["APP1035873"],"award-info":[{"award-number":["APP1035873"]}],"id":[{"id":"10.13039\/501100000923","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,3,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Cyclin-dependent kinase-like-5 (CDKL5) deficiency disorder (CDD) is a severe X-linked neurodegenerative disease characterised by early-onset epileptic seizures, low muscle tone, progressive intellectual disability and severe motor function. CDD affects \u223c1 in 60,000 live births, with many patients experiencing a reduced quality of life due to the severity of their neurological symptoms and functional impairment. There are no effective therapies for CDD, with current treatments focusing on improving symptoms rather than addressing the underlying causes of the disorder. Zebrafish offer many unique advantages for high-throughput preclinical evaluation of potential therapies for neurological diseases, including CDD. In particular, the large number of offspring produced, together with the possibilities for in vivo imaging and genetic manipulation, allows for the detailed assessment of disease pathogenesis and therapeutic discovery. We have characterised a loss-of-function zebrafish model for CDD, containing a nonsense mutation in cdkl5. cdkl5 mutant zebrafish display defects in neuronal patterning, seizures, microcephaly, and reduced muscle function caused by impaired muscle innervation. This study provides a powerful vertebrate model for investigating CDD disease pathophysiology and allowing high-throughput screening for effective therapies.<\/jats:p>\n                  <jats:p>This article has an associated First Person interview with the first author of the paper.<\/jats:p>","DOI":"10.1242\/dmm.049094","type":"journal-article","created":{"date-parts":[[2021,12,16]],"date-time":"2021-12-16T07:05:57Z","timestamp":1639638357000},"source":"Crossref","is-referenced-by-count":14,"title":["Novel preclinical model for CDKL5 deficiency disorder"],"prefix":"10.1242","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6549-8047","authenticated-orcid":false,"given":"Rita J.","family":"Serrano","sequence":"first","affiliation":[{"name":"School of Biological Sciences, Monash University, Melbourne 3800, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7170-5874","authenticated-orcid":false,"given":"Clara","family":"Lee","sequence":"additional","affiliation":[{"name":"School of Biological Sciences, Monash University, Melbourne 3800, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5739-3835","authenticated-orcid":false,"given":"Alon M.","family":"Douek","sequence":"additional","affiliation":[{"name":"Australian Regenerative Medicine Institute, Monash University, Melbourne 3800, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6207-1889","authenticated-orcid":false,"given":"Jan","family":"Kaslin","sequence":"additional","affiliation":[{"name":"Australian Regenerative Medicine Institute, Monash University, Melbourne 3800, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9501-8208","authenticated-orcid":false,"given":"Robert J.","family":"Bryson-Richardson","sequence":"additional","affiliation":[{"name":"School of Biological Sciences, Monash University, Melbourne 3800, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9745-3580","authenticated-orcid":false,"given":"Tamar E.","family":"Sztal","sequence":"additional","affiliation":[{"name":"School of Biological Sciences, Monash University, Melbourne 3800, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2022,3,8]]},"reference":[{"key":"2022030815263344500_DMM049094C1","doi-asserted-by":"publisher","first-page":"e54166","DOI":"10.1371\/journal.pone.0054166","article-title":"Validation of the zebrafish pentylenetetrazol seizure model: locomotor versus electrographic responses to antiepileptic drugs","volume":"8","author":"Afrikanova","year":"2013","journal-title":"PLoS ONE"},{"key":"2022030815263344500_DMM049094C2","doi-asserted-by":"publisher","first-page":"e91613","DOI":"10.1371\/journal.pone.0091613","article-title":"Mapping pathological phenotypes in a mouse model of CDKL5 disorder","volume":"9","author":"Amendola","year":"2014","journal-title":"PLoS ONE"},{"key":"2022030815263344500_DMM049094C3","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1159\/000331333","article-title":"CDKL5-related disorders: from clinical description to molecular genetics","volume":"2","author":"Bahi-Buisson","year":"2012","journal-title":"Mol. 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