title: CERKL knockdown causes retinal degeneration in zebrafish.
abstract: The human CERKL gene is responsible for common and severe forms of retinal dystrophies. Despite intense in vitro studies at the molecular and cellular level and in vivo analyses of the retina of murine knockout models, CERKL function remains unknown. In this study, we aimed to approach the developmental and functional features of cerkl in Danio rerio within an Evo-Devo framework. We show that gene expression increases from early developmental stages until the formation of the retina in the optic cup. Unlike the high mRNA-CERKL isoform multiplicity shown in mammals, the moderate transcriptional complexity in fish facilitates phenotypic studies derived from gene silencing. Moreover, of relevance to pathogenicity, teleost CERKL shares the two main human protein isoforms. Morpholino injection has been used to generate a cerkl knockdown zebrafish model. The morphant phenotype results in abnormal eye development with lamination defects, failure to develop photoreceptor outer segments, increased apoptosis of retinal cells and small eyes. Our data support that zebrafish Cerkl does not interfere with proliferation and neural differentiation during early developmental stages but is relevant for survival and protection of the retinal tissue. Overall, we propose that this zebrafish model is a powerful tool to unveil CERKL contribution to human retinal degeneration.
authors.affiliation: Departament de Genètica, Facultat de Biologia, Universitat de Barcelona, Barcelona, Spain.
authors.forename: Marina
authors.initials: M
authors.lastname: Riera
authors.forename: Demian
authors.initials: D
authors.lastname: Burguera
authors.forename: Jordi
authors.initials: J
authors.lastname: Garcia-Fernàndez
authors.forename: Roser
authors.initials: R
authors.lastname: Gonzàlez-Duarte
mesh_terms: D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D030801:Animals, Genetically Modified; D019556:COS Cells; D002522:Chlorocebus aethiops; D004625:Embryo, Nonmammalian / Q000196:embryology / Q000378:metabolism; D005123:Eye / Q000196:embryology / Q000254:growth & development / Q000378:metabolism; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D055785:Gene Knockdown Techniques; D006801:Humans; D017403:In Situ Hybridization; D008969:Molecular Sequence Data; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics / Q000378:metabolism*; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D012160:Retina / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D012162:Retinal Degeneration / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid; D015027:Zebrafish / Q000196:embryology / Q000235:genetics* / Q000254:growth & development; D029961:Zebrafish Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D020033:Protein Isoforms; D029961:Zebrafish Proteins; D017853:Phosphotransferases (Alcohol Group Acceptor); C585195:Cerkl protein, zebrafish