{"database": "metadata", "table": "run_metadata", "rows": [[34952, "SRR32472672", "SRX27786994", "SRS24165031", "SRP565999", "PRJNA1227535", "Characterization of a novel zebrafish model of MTMR5 associated Charcot Marie Tooth disease type 4B3", "GSE290354", "Transcriptome Analysis", "Biallelic loss of expression/function variants in MTMR5/SBF1 cause the inherited peripheral neuropathy Charcot Marie Tooth CMT Type 4B3. There is an incomplete understanding of the disease pathomechanisms underlying CMT4B3  and despite its severe clinical presentation  currently no disease modifying therapies. A key barrier to the study of CMT4B3 is the lack of pre clinical models that recapitulate the clinical and pathologic features of the disease. To address this barrier  we generated a zebrafish CRISPR/Cas9 mutant line with a full gene deletion of mtmr5. Resulting homozygous deletion zebrafish are born at normal Mendelian ratios and have preserved motor function. However  starting by 10 dpf  mutant zebrafish develop obvious morphometric changes in head size and brain volume. These changes are accompanied at the pathological level by abnormal axon outgrowths and by the presence of dysmyelination  changes reminiscent of the nerve pathology in human CMT4B3. Importantly  RNA sequencing from brain enriched samples identifies novel disease pathways including transcriptional changes in genes responsible for neurogenesis  chromatin remodeling/organization  and synaptic membrane homeostasis. Overall  our mtmr5 knockout zebrafish mirror genetic  clinical  and pathologic features of human CMT4B3. As such  it represents a first pre clinical model to phenocopy the disease  and an ideal tool for future studies on disease pathomechanisms and therapy development. Overall design: Bulk RNA sequencing of 7 dpf mtmr5 knockout and wild type brain enriched zebrafish samples. Four biological replicates were included from different breeding pairs over time.", null, "pubmed:40066109", null, "Brain enriched  wild type  biol rep1", "GSM8811130", null, "source name:head|tissue:head|genotype:wild type|geo loc name:missing|collection date:missing", "Brain enriched  wild type  biol rep1", "Adaptors trimmed using Trim Galore! Galaxy Version 0.6.7+galaxy0 Raw trimmed reads aligned to reference genome using RNA STAR Galaxy Version 2.7.11a+galaxy1 Filtered STAR alignments processed to extract raw read counts for genes using htseq count Galaxy Version 2.0.5+galaxy0 mode: intersection   nonempty Normalized count matrix was generated using DESeq2 v3.2 in R v4.4.0. Minimum expression cut off: 10 read counts in at least 3 samples. Assembly: GRCz11/Ensembl release 113 primary assembly  downloaded on October 21  2024. Supplementary files format and content: raw counts allSamples.csv includes raw counts for every gene for all samples Supplementary files format and content: normalized counts allSamples.csv includes normalized counts for genes above minimum expression cutoff for all samples", "head", null, "Zebrafish larvae were fin clipped and genotyped at 4 dpf 6 dpf. At 7 dpf  n=11 17 zebrafish heads were dissected per genotype  and immediately frozen at  80C. RNA extraction was performed for all samples 4x WT  and 4x mtmr5 KO using the RNeasy kit Qiagen. Quality control  RNA library preparation  cDNA synthesis  and library validation were performed by The Centre for Applied Genomics\u2014Next Generation Sequencing Facility PGCRL  The Hospital for Sick Children  Toronto.", "Zebrafish AB strain were raised and maintained at 28.5\u00b0C at the Zebrafish Facility at the Hospital for Sick Children  Toronto  ON  Canada. Zebrafish embryos were grown in blue water 0.3 g/L Instant Ocean  1 mg/L methylene blue  pH 7.0 from the one cell stage up to 7 dpf. All zebrafish procedures were performed in strict accordance with the Animals for Research Act of Ontario and the Guidelines of the Canadian Council on Animal Care.", "tissue:head|genotype:wild type", "GSM8811130", "GSM8811130: Brain enriched  wild type  biol rep1; Danio rerio; RNA Seq", "GSM8811130 r1", "GSM8811130", "1", "Zebrafish larvae were fin clipped and genotyped at 4 dpf 6 dpf. At 7 dpf  n=11 17 zebrafish heads were dissected per genotype  and immediately frozen at  80C. RNA extraction was performed for all samples 4x WT  and 4x mtmr5 KO using the RNeasy kit Qiagen. Quality control  RNA library preparation  cDNA synthesis  and library validation were performed by The Centre for Applied Genomics\u2014Next Generation Sequencing Facility PGCRL  The Hospital for Sick Children  Toronto.", null, "RNA-Seq", "TRANSCRIPTOMIC", "cDNA", "PAIRED", "ILLUMINA", "Illumina NovaSeq 6000", null, "SRP565999", null, null, "mtmr5_WT_1_S38_L002_R1_001.fastq.gz mtmr5_WT_1_S38_L002_R2_001.fastq.gz", "fastq fastq", 12280050236.0, 40662418.0, "GSM8811130 r1", "0:151 1:151", "A:3666524090;C:2479893988;G:2540363922;T:3593251867;N:16369", 151, 151, null, null, 3666524090, 2479893988, 2540363922, 3593251867, 16369, "SRX27786994", "SRS24165031", "SRA2083091", "Dowling Lab, Genetics & Genome Biology, Peter Gilgan Centre for Research and Learning", "Dowling Lab, Genetics & Genome Biology, Peter Gilgan Centre for Research and Learning", 2, 0.91363, 0.9138, 0.2442, 0.24267, 0.72232, 0.72123, 0.47864, 0.53039, 151, 151, "B", "B", "biological fallback assumption", "illumina", "novaseq_era", "unknown", "cdna_unspecified", "unknown", "bulk", "bulk", "bulk", null, "Canada", "2025-02-24", "Larval", "Larval", "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": ["34952"], "units": {}, "query_ms": 9.239926002919674}