title: Generation and characterization of FMR1 knockout zebrafish.
abstract: Fragile X syndrome (FXS) is one of the most common known causes of inherited mental retardation. The gene mutated in FXS is named FMR1, and is well conserved from human to Drosophila. In order to generate a genetic tool to study FMR1 function during vertebrate development, we generated two mutant alleles of the fmr1 gene in zebrafish. Both alleles produce no detectable Fmr protein, and produce viable and fertile progeny with lack of obvious phenotypic features. This is in sharp contrast to published results based on morpholino mediated knock-down of fmr1, reporting defects in craniofacial development and neuronal branching in embryos. These phenotypes we specifically addressed in our knock-out animals, revealing no significant deviations from wild-type animals, suggesting that the published morpholino based fmr1 phenotypes are potential experimental artifacts. Therefore, their relation to fmr1 biology is questionable and morpholino induced fmr1 phenotypes should be avoided in screens for potential drugs suitable for the treatment of FXS. Importantly, a true genetic zebrafish model is now available which can be used to study FXS and to derive potential drugs for FXS treatment.
authors: Hubrecht Institute, Royal Academy of Arts and Sciences and University Medical Center Utrecht, Utrecht, The Netherlands.
authors: Marjo J
authors: MJ
authors: den Broeder
authors: Herma
authors: H
authors: van der Linde
authors: Judith R
authors: JR
authors: Brouwer
authors: Ben A
authors: BA
authors: Oostra
authors: Rob
authors: R
authors: Willemsen
authors: René F
authors: RF
authors: Ketting
mesh_terms: D000483:Alleles; D000818:Animals; D030801:Animals, Genetically Modified; D001921:Brain / Q000378:metabolism; D005260:Female; D005821:Genetic Techniques; D006801:Humans; D017403:In Situ Hybridization; D051379:Mice; D008810:Mice, Inbred C57BL; D009154:Mutation; D009474:Neurons / Q000378:metabolism; D010641:Phenotype; D016601:RNA-Binding Proteins / Q000235:genetics* / Q000502:physiology*; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000235:genetics* / Q000502:physiology*; D051860:Fragile X Messenger Ribonucleoprotein 1
chemical_list: D016601:RNA-Binding Proteins; D029961:Zebrafish Proteins; C514430:Fmr1 protein, zebrafish; D051860:Fragile X Messenger Ribonucleoprotein 1