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We previously reported that <jats:italic>gba1<\/jats:italic> knockout (KO) medaka exhibited glucosylceramide accumulation and neuronopathic GD phenotypes, including short lifespan, the dopaminergic and noradrenergic neuronal cell loss, microglial activation, and swimming abnormality, with asyn accumulation in the brains. A recent study reported that deletion of GBA2, non-lysosomal glucocerebrosidase, in a non-neuronopathic GD mouse model rescued its phenotypes. In the present study, we generated <jats:italic>gba2<\/jats:italic> KO medaka and examined the effect of Gba2 deletion on the phenotypes of <jats:italic>gba1<\/jats:italic> KO medaka. The Gba2 deletion in <jats:italic>gba1<\/jats:italic> KO medaka resulted in the exacerbation of glucosylceramide accumulation and no improvement in neuronopathic GD pathological changes, asyn accumulation, or swimming abnormalities. Meanwhile, though <jats:italic>gba2<\/jats:italic> KO medaka did not show any apparent phenotypes, biochemical analysis revealed asyn accumulation in the brains. <jats:italic>gba2<\/jats:italic> KO medaka showed a trend towards an increase in sphingolipids in the brains, which is one of the possible causes of asyn accumulation. In conclusion, this study demonstrated that the deletion of Gba2 does not rescue the pathological changes or behavioral abnormalities of <jats:italic>gba1<\/jats:italic> KO medaka, and GBA2 represents a novel factor affecting asyn accumulation in the brains.<\/jats:p>","DOI":"10.1186\/s13041-021-00790-x","type":"journal-article","created":{"date-parts":[[2021,5,10]],"date-time":"2021-05-10T12:03:21Z","timestamp":1620648201000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Impact of Gba2 on neuronopathic Gaucher\u2019s disease and \u03b1-synuclein accumulation in medaka (Oryzias latipes)"],"prefix":"10.1186","volume":"14","author":[{"given":"Etsuro","family":"Nakanishi","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6251-0810","authenticated-orcid":false,"given":"Norihito","family":"Uemura","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hisako","family":"Akiyama","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masato","family":"Kinoshita","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sawamura","family":"Masanori","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yosuke","family":"Taruno","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hodaka","family":"Yamakado","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shu-ichi","family":"Matsuzawa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shunichi","family":"Takeda","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoshio","family":"Hirabayashi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ryosuke","family":"Takahashi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2021,5,10]]},"reference":[{"issue":"2","key":"790_CR1","doi-asserted-by":"publisher","first-page":"441","DOI":"10.3390\/ijms18020441","volume":"18","author":"J Stirnemann","year":"2017","unstructured":"Stirnemann J, Belmatoug N, Camou F, Serratrice C, Froissart R, Caillaud C, et al. 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