MOs resulted in abnormal axonal branching, changes in trigeminal ganglion number and craniofacial abnormalities. Most of these abnormalities in zebrafish embryos could be rescued using MPEP, an mGluR5 HC-067047 antagonist, or by fmr1 overexpression. In the present study, we generated two independent fmr1 knockout alleles using TILLING. TILLING combines random induced 153168-05-9 distributor mutations by ENU treatment and subsequent screening for null mutations. We provide a characterization of both homozygous and transheterozygous mutants with special emphasis on the phenotypic features reported earlier in the fmr1 knock-down study. We describe the generation of two fmr1 knockout alleles in zebrafish, and as such provide a new genetic model system to study FXS, a highly prevalent form of inherited mental retardation. FXS is caused by the loss of the gene product of fmr1, Fmr. FXS models have been described in multiple systems and from these models it has become clear that FMRP is acting at the synapse to regulate the translation of target mRNAs upon group 1 mGluR stimulation and whose protein products mediate synaptic strength. Fmr1 knock-out mice exhibit exaggerated translation of target mRNAs at the synapse. Potentially, such a process can be well affected by mGluR antagonists that would ameliorate the phenotypic outcome of FXS. Establishing a zebrafish model for FXS is very useful in this context, as the zebrafish embryo is amenable to large scale, small molecule drug screens. Supporting this idea was the finding that morpholino induced knock-down of fmr1 in the zebrafish led to embryonic phenotypes that could in principle be used as a read-out in drug screens. Tucker et al. reported neurite branching defects and changes in trigeminal ganglion neuron number following fmr1 knock down. Interestingly, treatment with MPEP, an mGluR5 antagonist, rescued most of these abnormalities, indicating a connection between mGluR5 signalling and fmr1 function in neurite branching and number of trigeminal ganglion neurons. Furthermore, it suggested that small molecule drug screens in the zebrafish may indeed be an affective manner of finding bio-active lead-compounds that are good starting points for developing drugs beneficial for FXS patients. Tuc