Expression of three zebrafish orthologs of human FMR1-related genes and their phylogenetic relationships
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The human fragile X mental retardation syndrome is caused by expansions of a CGG repeat in the FMR1 gene. FXR1 and FXR2 are autosomal paralogs of FMR1. The products of the three genes, FMRP, FXR1P, and FXR2P, respectively, belong to a family of RNA-binding proteins. While the FMR1-related gene family is well described in human, mouse and Drosophila, little is known about zebrafish (Danio rerio) orthologs of these genes. Here we collate the known FMR1-related gene sequences from zebrafish, examine their regions of structural conservation, and define their orthologies with the human genes. We demonstrate that zebrafish possess only three FMR1-related genes, fmr1, fxr1 and fxr2, and these are orthologous to the human FMR1, FXR1 and FXR2 genes respectively. We examine the spatiotemporal pattern of transcription of the zebrafish genes from 0 hours post fertilisation (hpf) until 24 hpf. Expression of fmr1, fxr1 and fxr2 is widespread throughout this time. However, relative to surrounding tissues, expression of fxr2 is raised in adaxial and somitic cells by 12 hpf while fxr1 expression is high in the anterior of the embryo, and is raised in adaxial cells by 12 hpf. Distinct patterns (and levels) of expression are seen for the different genes later in development. At 24 hpf, fxr1 and fxr2 transcripts show complex distribution patterns in somites. The expression of the FMR1-related gene family in zebrafish tissues is broadly consistent with expression in mouse and human, supporting the idea that zebrafish should be an excellent model organism in which to study the functions of the vertebrate FMR1-related gene family.
KeywordsDanio rerio fmr1 fxr1 fxr2
We thank Sonia Dayan for her assistance in performing the Real-Time quantitative RT-PCR. This research made possible by a grant from the Australian Research Council through the Special Research Centre for the Molecular Genetics of Development (CMGD).
This research was carried out under the auspices of the Animal Ethics Committee of The University of Adelaide.
- Bontekoe CJ, McIlwain KL, Nieuwenhuizen IM, Yuva-Paylor LA,Nellis A, Willemsen R, Fang Z, Kirkpatrick L, Bakker CE, McAninch R, Cheng NC, Merriweather M, Hoogeveen AT, Nelson D, Paylor R, Oostra BA (2002) Knockout mouse model for Fxr2: a modelfor mental retardation. Hum Mol Genet 11(5):487–498CrossRefPubMedGoogle Scholar
- Brown W (2002) The molecular biology of the fragile X mutation. In: Hagerman RJ, Hagerman PJ, Baltimore MD (eds) Fragile X syndrome diagnosis, treatment, and research. Johns Hopkins University Press, Baltimore, Md., pp 110–135Google Scholar
- Felsenstein J (1989) PHYLIP—phylogeny inference package (version 3.2). Cladistics 5:164–166Google Scholar
- Jin P, Zarnescu DC, Zhang F, Pearson CE, Lucchesi JC, Moses K, Warren ST, Hagerman RJ, Leehey M, Heinrichs W et al (2003) RNA-mediated neurodegeneration caused by the fragile X premutation rCGG repeats in Drosophila Intention tremor, Parkinsonism, and generalized brain atrophy in male carriers of fragile X. Neuron 39:739–747CrossRefPubMedGoogle Scholar
- Jowett T (1997) Tissue in situ hybridization. Wiley, New YorkGoogle Scholar
- Nicholas KB, Nicholas HB Jr, Deerfield DW II (1997) GeneDoc: analysis and visualization of genetic variation. EMBNEW News 4:1–4Google Scholar
- Tamanini F, Kirkpatrick LL, Schonkeren J, van Unen L, Bontekoe C,Bakker C, Nelson DL, Galjaard H, Oostra BA, HoogeveenAT (2000) The fragile X-related proteins FXR1P and FXR2P contain afunctional nucleolar-targeting signal equivalent to the HIV-1 regulatoryproteins. Hum Mol Genet 9(10):1487–1493CrossRefPubMedGoogle Scholar
- Verkerk AJ, Pieretti M, Sutcliffe JS, Fu YH, Kuhl DP, Pizzuti A, Reiner O, Richards S, Victoria MF, Zhang FP et al (1991) Identification of a gene (FMR-1) containing a CGG repeat coincident with a breakpoint cluster region exhibiting length variation in fragile X syndrome. Cell 65:905–914CrossRefPubMedGoogle Scholar