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Here we investigate the knockdown efficiency of three synthetic miRNA-expressing backbones and show that these constructs can downregulate a sensor transgene with different degrees of potency. Using this approach, we reproduce spinal muscular atrophy (SMA) in zebrafish by targeting the <jats:italic>smn1<\/jats:italic> gene. We also generate different transgenic lines, with severity and age of onset correlated to the level of <jats:italic>smn1<\/jats:italic> inhibition, recapitulating for the first time the different forms of SMA in zebrafish. These lines are proof-of-concept that miRNA-based approaches can be used to generate potent heritable gene knockdown in zebrafish.<\/jats:p>","DOI":"10.1038\/ncomms8378","type":"journal-article","created":{"date-parts":[[2015,6,8]],"date-time":"2015-06-08T10:10:38Z","timestamp":1433758238000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":47,"title":["Effective heritable gene knockdown in zebrafish using synthetic microRNAs"],"prefix":"10.1038","volume":"6","author":[{"given":"Jean","family":"Giacomotto","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silke","family":"Rinkwitz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas S.","family":"Becker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2015,6,8]]},"reference":[{"key":"BFncomms8378_CR1","doi-asserted-by":"publisher","first-page":"353","DOI":"10.1038\/nrg2091","volume":"8","author":"GJ Lieschke","year":"2007","unstructured":"Lieschke, G. 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