title: Characterisation of Fmrp in zebrafish: evolutionary dynamics of the fmr1 gene.
abstract: Fragile X syndrome is the most common inherited form of mental retardation. It is caused by the lack of the Fragile X Mental Retardation Protein (FMRP), which is encoded by the FMR1 gene. Although Fmr1 knockout mice display some characteristics also found in fragile X patients, it is a complex animal model to study brain abnormalities, especially during early embryonic development. Interestingly, the ortholog of the FMR1 gene has been identified not only in mouse, but also in zebrafish (Danio rerio). In this study, an amino acid sequence comparison of FMRP orthologs was performed to determine the similar regions of FMRP between several species, including human, mouse, frog, fruitfly and zebrafish. Further characterisation of Fmrp has been performed in both adults and embryos of zebrafish using immunohistochemistry and western blotting with specific antibodies raised against zebrafish Fmrp. We have demonstrated a strong Fmrp expression in neurons of the brain and only a very weak expression in the testis. In brain tissue, a different distribution of the isoforms of Fmrp, compared to human and mouse brain tissue, was shown using western blot analysis. Due to the high similarity between zebrafish Fmrp and human FMRP and their similar expression pattern, the zebrafish has great potential as a complementary animal model to study the pathogenesis of the fragile X syndrome, especially during embryonic development.
authors.affiliation: Department of Clinical Genetics, Erasmus MC, P.O. Box 1738, 3000 DR Rotterdam, The Netherlands.
authors.forename: Sandra
authors.initials: S
authors.lastname: van 't Padje
authors.forename: Bart
authors.initials: B
authors.lastname: Engels
authors.forename: Lau
authors.initials: L
authors.lastname: Blonden
authors.forename: Lies-Anne
authors.initials: LA
authors.lastname: Severijnen
authors.forename: Frans
authors.initials: F
authors.lastname: Verheijen
authors.forename: Ben A
authors.initials: BA
authors.lastname: Oostra
authors.forename: Rob
authors.initials: R
authors.lastname: Willemsen
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015153:Blotting, Western; D001923:Brain Chemistry / Q000235:genetics; D019556:COS Cells; D002522:Chlorocebus aethiops; D017124:Conserved Sequence; D004625:Embryo, Nonmammalian; D019143:Evolution, Molecular; D051860:Fragile X Messenger Ribonucleoprotein 1; D005600:Fragile X Syndrome; D018507:Gene Expression Regulation, Developmental; D007150:Immunohistochemistry; D023421:Models, Animal; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000235:genetics*; D019913:Nuclear Localization Signals / Q000235:genetics; D017434:Protein Structure, Tertiary; D016601:RNA-Binding Proteins / Q000737:chemistry / Q000235:genetics*; D017386:Sequence Homology, Amino Acid; D012689:Sequence Homology, Nucleic Acid; D014162:Transfection; D015027:Zebrafish / Q000196:embryology / Q000235:genetics*
chemical_list: D051860:Fragile X Messenger Ribonucleoprotein 1; D009419:Nerve Tissue Proteins; D019913:Nuclear Localization Signals; D016601:RNA-Binding Proteins