{"database": "metadata", "table": "run_metadata", "rows": [[33620, "SRR30310488", "SRX25770931", "SRS22407034", "SRP527479", "PRJNA1150074", "Epileptic phenotypes in slc13a5 loss of function zebrafish are rescued by blocking NMDA receptor signaling", "GSE275235", "Transcriptome Analysis", "SLC13A5 encodes a citrate transporter highly expressed in the brain important for regulating intra  and extracellular citrate levels. Mutations in this gene cause a rare infantile epilepsy characterized by lifelong seizures  developmental delays  behavioral deficits  poor motor progression  and language impairments. SLC13A5 individuals respond poorly to treatment options; yet drug discovery programs are limited due to a paucity of animal models that phenocopy human symptoms. Here  we used CRISPR/Cas9 to create loss of function mutations in slc13a5a and slc13a5b  the zebrafish paralogs to human SLC13A5. slc13a5 mutant larvae showed cognitive dysfunction and sleep disturbances  consistent with SLC13A5 individuals. These mutants also exhibited fewer neurons and a concomitant increase in apoptosis across the optic tectum  a region important for sensory processing. slc13a5 mutants displayed hallmark features of epilepsy  including an imbalance in glutamatergic and GABAergic excitatory inhibitory gene expression  disrupted neurometabolism  and neuronal hyperexcitation as measured in vivo by extracellular field recordings and live calcium imaging. Mechanistically  we tested the involvement of NMDA signaling in slc13a5 mutant epilepsy like phenotypes. Slc13a5 protein co localizes with excitatory NMDA receptors in wild type zebrafish and blocking NMDA receptors in slc13a5 mutant larvae rescued bioenergetics  hyperexcitable calcium events  and behavioral defects. These data provide empirical evidence in support of the hypothesis that excess extracellular citrate over chelates the ions needed to regulate NMDA receptor function  leading to sustained channel opening and an exaggerated excitatory response that manifests as seizures. These data show the utility of slc13a5 mutant zebrafish for studying SLC13A5 epilepsy and open new avenues for drug discovery. Overall design: 5 dpf zebrafish heads were pooled to generate three biological replicates of each group. Four groups of samples were generated: WT controls  5a mutants  5b mutants and 5a/5b double mutants", null, "pubmed:40208862", null, "DM biol rep 2", "GSM8473258", null, "source name:heads|tissue:heads|genotype:5a / ;5b / |treatment:untreated|geo loc name:missing|collection date:missing", "DM biol rep 2", "Fastq files were aligned using STAR and gene counts obtained from STAR were given as input to DESeq2 for differential gene analysis and obtained normalised counts. Genes with zero values in more than 4 samples were exlcuded from the analysis Assembly: GRCz11 Supplementary files format and content: tab delimited text file include raw counts for each sample Supplementary files format and content: tab delimited text file include log normalised counts for each sample", "heads", "untreated", "Trizol based RNA extraction and column purification purified RNA with RIN>7 were sent for sequencing NextSeq2000 P2 100 cycle", "Adult zebrafish TL and AB strains were maintained at 28\u00b0C in a 14 hour light/10 hour dark cycle under standard aquaculture conditions  and fertilized eggs were collected via natural spawning.", "tissue:heads|genotype:5a / ;5b / |treatment:untreated", "GSM8473258", "GSM8473258: DM biol rep 2; Danio rerio; RNA Seq", "GSM8473258 r1", "GSM8473258", "1", "Trizol based RNA extraction and column purification purified RNA with RIN>7 were sent for sequencing NextSeq2000 P2 100 cycle", null, "RNA-Seq", "TRANSCRIPTOMIC", "cDNA", "PAIRED", "ILLUMINA", "NextSeq 2000", null, "SRP527479", null, null, "Li47813-DM2_S5_R2_001.fastq.gz Li47813-DM2_S5_R1_001.fastq.gz", "fastq fastq", 5030260806.0, 41607672.0, "GSM8473258 r1", "0:60.47 1:60.43", "A:1291665135;C:1198581962;G:1206075180;T:1323425262;N:10513267", 60, 60, null, null, 1291665135, 1198581962, 1206075180, 1323425262, 10513267, "SRX25770931", "SRS22407034", "SRA1951631", "Kurrasch Lab, Department of Medical Genetics, University of Calgary", "Kurrasch Lab, Department of Medical Genetics, University of Calgary", 2, 0.94958, 0.95221, 0.08402, 0.0824, 0.64628, 0.64553, 0.47628, 0.47968, 61, 60, "B", "B", "biological fallback assumption", "illumina", "nextseq_v2", "unknown", "cdna_unspecified", "unknown", "bulk", "unknown", "unknown", null, "Canada", "2024-08-20", "Adult", "Adult", "Head", "Nervous System"]], "columns": ["rowid", "run.accession", "experiment.accession", "sample.accession", "study.accession", "bioproject", "study.title", "study.alias", "study.type", "study.abstract", "study.attributes", "study.PMIDs", "sample.description", "sample.title", "sample.alias", "sample.centername", "sample.attributes", "GEOsample.title", "GEOsample.dataprocessing", "GEOsample.source", "GEOsample.treatmentprotocol", "GEOsample.extractprotocol", "GEOsample.growthprotocol", "GEOsample.characteristics", "GEOsample.accession", "experiment.title", "experiment.alias", "experiment.library_name", "experiment.design_description", "experiment.library_construction_protocol", "experiment.attributes", "experiment.library_strategy", "experiment.library_source", "experiment.library_selection", "experiment.library_layout", "experiment.platform", "experiment.instrument_model", "experiment.spot_descriptor", "experiment.study_ref", "run.title", "run.attributes", "run.filename", "run.semantic_name", "run.total_bases", "run.total_spots", "run.alias", "run.read_lengths", "run.base_counts", "run.r1_length", "run.r2_length", "run.r3_length", "run.r4_length", "run.Acount", "run.Ccount", "run.Gcount", "run.Tcount", "run.Ncount", "run.experiment", "run.pool_member", "submission.accession", "submission.srasource", "submission.bioprojectsource", "seqdetective.n_mates", "seqdetective.mapping_rate.mate1", "seqdetective.mapping_rate.mate2", "seqdetective.nofeature_rate.mate1", "seqdetective.nofeature_rate.mate2", "seqdetective.sparsity.mate1", "seqdetective.sparsity.mate2", "seqdetective.pos_strand_rate.mate1", "seqdetective.pos_strand_rate.mate2", "seqdetective.readlen.mate1", "seqdetective.readlen.mate2", "seqdetective.judgement.mate1", "seqdetective.judgement.mate2", "seqdetective.judgement.reason", "platform_family", "instrument_generation", "read_bias", "selection_class", "prep_kit", "sc_or_bulk", "tech_class", "technology", "tech_variant", "submission.bioprojectsource.country", "earliest_date", "devstage_curation", "devstage_curation_coarse", "tissue_curation", "tissue_curation_coarse"], "primary_keys": ["rowid"], "primary_key_values": ["33620"], "units": {}, "query_ms": 9.811458003241569}