Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA358410 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR5124081_1.fastq.gz | Fastqsanger.gz | |||
| SRR5124081_2.fastq.gz | Fastqsanger.gz | |||
| SRR5124082_1.fastq.gz | Fastqsanger.gz | |||
| SRR5124082_2.fastq.gz | Fastqsanger.gz | |||
| SRR5124083_1.fastq.gz | Fastqsanger.gz |
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Project description:Uromodulin is the most abundant urinary protein. It is exclusively produced and released in the urine by renal epithelial cells lining the thick ascending limb of Henle’s loop (TAL). Mutations in UMOD, the gene encoding uromodulin, cause autosomal dominant tubulointerstitial kidney disease uromodulin-related (ADTKD-UMOD). While the primary effect of all mutations, retention in the endoplasmic reticulum (ER), is well established, its downstream effects are still unknown. The aim of this study was to gain insight into ADTKD-UMOD pathogenesis through transcriptional profiling of immortalised mouse TAL cells (mTAL) transduced with lentiviral vectors encoding wild type or mutant (C150S) GFP-tagged human uromodulin.
2017-05-04 | GSE92704 | GEO
Project description:Uromodulin (UMOD) is a secreted glycoprotein exclusively expressed by the cells lining the thick ascending limb of the loop of henle and the early distal tubule of the kidney nephron. Mutations in UMOD that interfere with proper folding of the protein are responsible for a progressive form of interstitial fibrotic kidney disease that leads to end stage renal disease, referred to as Uromodulin Associated Kidney Disease (UAKD). To assess key transcriptional changes associated with the progression of UAKD, we generated a knock-in mouse model harboring the mouse equivalent of the human mutation C148W. We profiled both the whole kidney tissue, as well as the specific UMOD+ cell populaitons in mutant and wild type mice. Analysis of differentially expressed genes in whole tissue and UMOD+ cells revealed a strong TNF-signaling signature, as well as TRIB3 upregulation, which is a key mediator of the intrinsic ER-stress mediated cell death pathway.
2017-09-01 | GSE102566 | GEO
Project description:Background: Uromodulin (Tamm-Horsfall) protein is secreted by the thick ascending limb into urine and crosses the basolateral membrane into the kidney interstitium and blood. Uromodulin may engage the kidney’s innate immune system with pro and anti-inflammatory effects described. Mutations in the UMOD gene are a cause of autosomal dominant tubulointerstitial kidney disease (ADTKD) due to protein misfolding and endoplasmic reticulum stress. We identified a family with a UMOD mutation (C106F) that leads to glomerular and interstitial inflammation atypical for ADTKD. Methods: To determine if the observed phenotype is due to mutant uromodulin induced changes in the innate or adaptive immune system, we developed a transgenic (tg) mouse with a homologous cysteine to phenylalanine mutation (C105F) in the UMOD gene using CRISPR-Cas9 gene editing. Results: LLC-PK1 cells expressing wt and mutant protein had increased basolateral secretion of protein compared with cells expressing wt or mutant protein alone. EM examination of mutant medium showed protein aggregates in contrast to filaments in wt medium. Immunoprecipitation of plasma uromodulin from mutant mice demonstrated aggregate formation not seen in wt mice. Tg/+ mice displayed increased F4/80+ mononuclear phagocyte (MP) and podocyte inflammasome activity at baseline. Tg/+ mice developed glomerular and interstitial matrix deposition, myofibroblast proliferation and increased Creatinine with aging. Following ischemia-reperfusion injury, tg/+ mice had no increase in inflammasome activation over baseline in contrast to wt littermates and displayed improved tubular repair and renal function at 7 days. Differential gene expression analysis by RNA sequencing of kidney MP revealed activation of the ATF4 mediated stress response pathway and genes associated with the development of tissue fibrosis. Conclusions: The C106F mutation results in glomerular and interstitial inflammatory kidney disease due to interaction of aggregated misfolded protein with mononuclear phagocytic cells resulting in ER stress response. The resulting alteration in the immune system leads to improved kidney repair following acute injury but fibrosis and chronic renal failure with aging.
2020-08-23 | GSE139585 | GEO
Project description:<p>Although multi-agent combination chemotherapy is curative in a significant fraction of childhood acute lymphoblastic leukemia (ALL) patients, 20% of cases relapse and most die due to chemo-refractory disease. Here we used whole-exome and whole-genome sequencing to analyze the mutational landscape and pattern of clonal evolution at relapse in pediatric ALL cases. These analyses showed that ALL relapses originate from a common ancestral precursor clone of the diagnosis and relapsed populations and frequently harbor mutations implicated in chemotherapy resistance. RAS-MAPK pathway activating mutations in NRAS, KRAS and PTPN11 were present in 24/55 (44%) cases in our series. Notably, while some cases showed emergence of RAS mutant clones at relapse, in others, RAS mutant clones present at diagnosis were replaced by RAS wild type populations. Mechanistically, functional dissection of mouse and human wild type Kras and mutant Kras (Kras G12D) isogenic leukemia cells demonstrated induction of methotrexate resistance, but also improved response to vincristine, in mutant Kras- expressing lymphoblasts. These results identify chemotherapy driven selection as a central mechanism of leukemia clonal evolution and pave the road for the development of tailored personalized therapies for the treatment of relapsed ALL. </p>
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Project description:Transcriptional profiling of HOMC-D4 immortalized mesothelial cell lines expressing wild type TAZ or activated S89A mutant TAZ
2018-08-31 | GSE115738 | GEO
Project description:To gain insight into autosomal dominant tubulointerstitial kidney disease (ADTKD)-uromodulin (UMOD) pathophysiology, we carried out transcriptional profiling of kidneys from 1- and 2-month-old TgUmodC147W mice, a transgenic model that recapitulates the main features of the disease, and TgUmodwt mice, a matched transgenic control of Umod overexpression. These time points correspond to presymptomatic stages that precede renal dysfunction in TgUmodC147W mice.
2017-08-18 | GSE97093 | GEO
Project description:Transcriptional profiling of transformed Ba/F3 cells by myeloproliferative neoplasm-associated JAK2 V617F mutant comparing control Ba/F3 cells expressing wild type JAK2.
2013-10-31 | GSE34239 | GEO
Project description:Uromodulin-associated kidney disease (UAKD) summarizes different clinical features of an autosomal dominant heritable disease syndrome in humans with a proven uromodulin (UMOD) mutation involved. It is often characterized by hyperuricemia, gout, alteration of urine concentrating ability, as well as a variable rate of disease progression inconstantly leading to renal failure and histological alterations of the kidneys. We recently established the two Umod mutant mouse lines UmodC93F and UmodA227T on the C3H inbred genetic background both showing kidney defects analogous to those found in human UAKD patients. The aim of this study was the further analysis of the phenotypic alterations by examining the kidneys as primarily affected organs. Transcriptome and quantitative PCR analyses as well as IHC analyses found significant changes related to the phenotyping changes. 4 male mice of each mutant cohort (Umod C93F & Umod A227T) and the corresponding wildtype controls, each mutant mouse was compared to the mean of the corresponding wildtype including a technical replicate (dye swap)
2014-10-01 | E-GEOD-58513 | biostudies-arrayexpress
Project description:RNAseq data from mouse beta-cells expressing mutant (GCK Y214C) versus wild-type Glucokinase
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Project description:Transcriptional profiling of Rhodopseudomonas palustris (R. palustris) comparing cbbT1 over-expressing strain with cbbT2 over-expressing strain. Goal was to discriminate the molecular mechanisms between transketolase I (cbbT1) and transketolase II (cbbT2). R.palustris is a purple non-sulfur anoxygenic phototrophic bacterium and transketolase (cbbT1 and cbbT2) is a key enzyme involved in the CBB cycle. Here, we investogated the functions of transketolase isoforms I (cbbT1) and II (cbbT2) in R. palustris through transcriptional profiling and other functional assays. Four-condition experiment, cbbT1 over-expressing cells, cbbT2 over-expressing cells, Negative control strain with empty plasmid, Wild type strain.
2014-05-06 | E-GEOD-29310 | biostudies-arrayexpress