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A founder mutation in the human endolysosomal trafficking protein <jats:italic>VPS11<\/jats:italic> has been identified in Ashkenazi Jewish patients manifesting classic gLE symptoms of hypomyelination, developmental delay, motor and systemic deficits. In this study, we characterized the visual and sensorimotor function of two zebrafish <jats:italic>vps11<\/jats:italic> mutant lines: the previously reported <jats:italic>vps11(plt)<\/jats:italic>, and a new <jats:italic>vps11<\/jats:italic>(\u2212\/\u2212) null mutant line, using behavioral analysis to track larval motor responses to visual and acoustic stimuli. We found that mutant larvae from both <jats:italic>vps11<\/jats:italic>(<jats:italic>plt<\/jats:italic>) and <jats:italic>vps11<\/jats:italic>(\u2212\/\u2212) lines were able to visually distinguish light and dark, but showed a progressive loss of a normal sensorimotor response to visual stimuli from 5\u00a0days post fertilization (dpf) to 7dpf. Additionally, optokinetic response analysis performed at 5dpf indicated that the mutants were significantly visually impaired. Both mutant lines also displayed a progressively lower sensorimotor response to a singular acoustic stimulus from 5-7dpf. Next, we tested the habituation response of the mutant lines to series of acoustic taps. We found both mutant lines habituated faster than their siblings, and that <jats:italic>vps11(plt)<\/jats:italic> mutants habituated faster than the <jats:italic>vps11<\/jats:italic>(\u2212\/\u2212) mutants. Together, these data suggest that loss of Vps11 function results in progressive visual and sensorimotor abnormalities in the zebrafish <jats:italic>vps11(plt)<\/jats:italic> and <jats:italic>vps11<\/jats:italic>(\u2212\/\u2212) mutant lines. This is the first study to characterize behavioral deficits in a vertebrate model of Vps11-dependent gLE. The mutants and behavioral assays described here could be a valuable model system in which to test potential pharmacological interventions for gLE.<\/jats:p>","DOI":"10.1038\/s41598-022-07448-1","type":"journal-article","created":{"date-parts":[[2022,3,3]],"date-time":"2022-03-03T11:05:35Z","timestamp":1646305535000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Vision and sensorimotor defects associated with loss of Vps11 function in a zebrafish model of genetic leukoencephalopathy"],"prefix":"10.1038","volume":"12","author":[{"given":"Shreya","family":"Banerjee","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lillian E.","family":"Ranspach","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xixia","family":"Luo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauren T.","family":"Cianciolo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph","family":"Fogerty","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian D.","family":"Perkins","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryan","family":"Thummel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,3,3]]},"reference":[{"key":"7448_CR1","doi-asserted-by":"publisher","first-page":"494","DOI":"10.1016\/j.ymgme.2015.01.006","volume":"114","author":"A Vanderver","year":"2015","unstructured":"Vanderver, A. et al. 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