Mutations in ClC-5 cause Dent's disease, a disorder associated with low molecular weight proteinuria, hyperphosphaturia and kidney stones. ClC-5 is a Cl /H+-exchanger predominantly expressed in the kidney, where it facilitates the acidification of proximal tubular endosomes. The reduction in proximal tubular endocytosis resulting from a lack of ClC-5 raises the luminal concentration of filtered proteins and peptides like PTH.<br></br><br></br> We used gene expression profiling to identify possible signaling pathways that might be changed in ClC-5 KO kidneys, bones and intestines. Mouse model described in Piwon et al, ClC-5 Cl--channel disruption impairs endocytosis in a mouse model for Dent's disease, Nature 408, 369-373 (16 November 2000),doi: 10.1038/35042597
Kidney-specific upregulation of vitamin D3 target genes in ClC-5 KO mice.
Sex, Age, Specimen part, Subject
View SamplesDifferent from canonical ubiquitin-like proteins, Hub1 does not form covalent conjugates with substrates but binds proteins non-covalently. In Saccharomyces cerevisiae, Hub1 associates with spliceosomes and mediates alternative splicing of SRC1, without affecting pre-mRNA splicing generally. Human Hub1 is highly similar to its yeast homolog, but its cellular function remains largely unexplored. Here, we show that human Hub1 binds to the spliceosomal protein Snu66 as in yeast, however, unlike its S. cerevisiae homolog, human Hub1 is essential for viability. Prolonged in vivo depletion of human Hub1 leads to various cellular defects, including splicing speckle abnormalities, partial nuclear retention of mRNAs, mitotic catastrophe and consequently cell death by apoptosis. Early consequences of Hub1 depletion are severe splicing defects, however, only for specific splice sites leading to exon skipping and intron retention. Thus, the ubiquitin-like protein Hub1 is not a canonical spliceosomal factor needed generally for splicing, but rather a modulator of spliceosome performance and facilitator of alternative splicing.
The conserved ubiquitin-like protein Hub1 plays a critical role in splicing in human cells.
Cell line
View SamplesClC-2 is a broadly expressed Cl- channel of the CLC family of Cl- channels and transporters which is abundantly expressed in brain. Here it was proposed to participate in lowering the cytoplasmic Cl- concentration of neurons, a process that establishes an inhibitory response to the neurotransmitters GABA and glycine (Staley et al., 1996). Heterozygous mutations in CLCN2 (the gene encoding ClC-2) were recently reported in a few patients with three clinically distinct forms of epilepsy (Haug et al, 2003). However, the disruption of ClC-2 in mice (ClC-2 KO mouse) did not entail epilepsy (Bösl et al., 2001; Nehrke et al., 2002) but myelin vacuolation in fiber tracts of the central nervous system. We used a gene expression profiling of the ClC-2 KO mouse in brain to identify possible disease mechanism which cause the observed myelin phenotype. As these myelin vacuolation became apparent in the fiber tracts of ClC-2 KO cerebellum at P28 and increased with age, we analysed the cerebellum of ClC-2 KO mice at different postnatal ages, before (P14) and after (P35) the KO cerebellum has been affected by myelin vacuolation.
Leukoencephalopathy upon disruption of the chloride channel ClC-2.
Sex, Age, Specimen part, Subject, Time
View Samples3 pairs of wt and ClC-6 knockout mice, RNA from p14 hippocampus
Lysosomal storage disease upon disruption of the neuronal chloride transport protein ClC-6.
Sex, Age, Specimen part, Subject, Time
View SamplesCaesarean-delivered preterm pigs were fed 3 d of parenteral nutrition followed by 2 d of enteral formula feeding. Antibiotics (n=11) or control saline (n=13) were given twice daily from birth to tissue collection at d 5. NEC-lesions and intestinal structure, function, microbiology and immunity markers were recorded.
Antibiotics modulate intestinal immunity and prevent necrotizing enterocolitis in preterm neonatal piglets.
Specimen part, Treatment
View SamplesBACKGROUND
Emmprin and survivin predict response and survival following cisplatin-containing chemotherapy in patients with advanced bladder cancer.
No sample metadata fields
View SamplesProjection-dependent ribosome profling from mouse mPFC.
Molecular and Circuit-Dynamical Identification of Top-Down Neural Mechanisms for Restraint of Reward Seeking.
Specimen part
View SamplesUsing anti-Argonaute (anti-AGO) antibody co-immunoprecipitation, followed by microarray analyses and downstream bioinformatics, RIP-Chip experiments enable direct analyses of miRNA targets. The analyses support four major findings: (i) RIP-Chip studies correlated with total input mRNA profiling provides more comprehensive information than using either RIP-Chip or total mRNA profiling alone after miRNA transfections; (ii) new data confirm that miR-107 paralogs target coding sequence (CDS) of mRNA; (iii) biochemical and computational studies indicate that the 3 portion of miRNAs plays a role in guiding miR-103/7 to the CDS of targets; and (iv) there are major sequence-specific targeting differences between miRNAs in terms of CDS versus 3-untranslated region targeting, and stable AGO association versus mRNA knockdown. For detailed protocol and for full discussion of the results please see Nelson PT et al, Nucleic Acids Res. 2011 Oct;39(18):8163-72.
Specific sequence determinants of miR-15/107 microRNA gene group targets.
Specimen part, Disease, Cell line
View SamplesThe goal of this study is to identify downstream pathways, diagnostic markers, and potential therapeutic targets for IFS/CMN.
Mediators of receptor tyrosine kinase activation in infantile fibrosarcoma: a Children's Oncology Group study.
Specimen part
View SamplesCellular RNA levels are determined by transcription and decay rates, which are fundamental in understanding gene expression regulation. Measurement of these two parameters is usually performed independently, complicating analysis and introducing methodological biases that hamper direct comparison. Here, we present a simple approach of concurrent sequencing of S. cerevisiae polyA+ and polyA- RNA 3' ends to simultaneously estimate total RNA levels, transcription and decay rates from the same RNA sample. The transcription data generated correlate well with reported estimates and also reveal local RNA polymerase stalling and termination sites with high precision. Although the method by design uses brief metabolic labeling of newly synthesized RNA with 4-thiouridine, the results demonstrate that transcription estimates can also be gained from unlabeled RNA samples. These findings underscore the potential of the approach, which should be generally applicable to study a range of biological questions in diverse organisms. Overall design: RNA 3' end seq of total and 2min 4-thiouracil (4tU) labelled RNA from S. cerevisiae cells. Aliquots of RNA were directly subjected to pA+ RNA 3' end sequencing (noPap samples). A second aliquot was in vitro polyadenylated using E. coli poly(A) polymerase and ribodepleted before library preparation (xPap samples).
Simultaneous Measurement of Transcriptional and Post-transcriptional Parameters by 3' End RNA-Seq.
Cell line, Subject
View Samples