Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA271334 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:The mouse Ikaros-deficient thymic lymphoma cell line T29 was transduced with a retrovirus expressing an fusion protein between a dominant-negative form of Mastermind and the ligand binding domain of the estrogen receptor. Cells trreated with Ethanol or 4-hydroxy-tamoxyfen for 24h were profiled.
2013-04-17 | GSE46089 | GEO
Project description:The mouse Ikaros-deficient thymic lymphoma cell line T29 was transduced with an empty retrovirus (MigR1) or a retrovirus expressing an fusion proein between Ikaros1 and the ligand binding domain of the estrogen receptor. Cells trreated with ethanol or 4-hydroxy-tamoxyfen (4OHT) for 24h were profiled.
2013-04-17 | GSE46088 | GEO
Project description:Background: Severe combined immunodeficiency (SCID) is characterized by arrested T lymphocyte production and B lymphocyte dysfunction, resulting in life-threatening infections. Early diagnosis of SCID through population-based newborn screening (NBS) optimizes clinical management and outcomes, and also permits identification of previously unknown factors essential for human lymphocyte development. Methods: SCID was detected, prior to onset of infections, by NBS of T cell receptor excision circles, a biomarker for thymic output. Upon confirmation, the affected baby was treated by allogeneic hematopoietic cell transplantation (HCT). The genetic cause was sought by exome sequencing of the patient and parents, followed by functional analysis of a prioritized candidate gene using human hematopoietic stem cells (HSC) and zebrafish embryos. Results: An infant with leaky SCID, craniofacial and dermal abnormalities, and absent corpus callosum had his immune deficit fully corrected by HCT. Exome sequencing revealed a heterozygous, de novo, missense mutation pN441K in BCL11B. The mutant Bcl11b protein had dominant negative activity, abrogating the ability of wild type Bcl11b to bind DNA, arresting T cell lineage development and disrupting HSC migration, revealing a novel function of Bcl11b. The patientâs defects, recapitulated in Bcl11b-deficient zebrafish, were reversed by ectopic expression of intact, but not mutant, human BCL11B. Conclusions: Newborn screening facilitated treatment and identification of a novel etiology for human SCID. Coupling exome sequencing with candidate gene evaluation in human HSC and in zebrafish revealed that a constitutional BCL11B mutation causes human multisystem anomalies with SCID, while also revealing a novel, pre-thymic role for Bcl11b in hematopoietic progenitors. 3 samples were analyzed in duplicate, Sample 1 was human HSC transduced with GFP only lentivirus which served as controls, Sample 2 was human HSC transduced with lentivirus expressing FLAG-tagged WT BCL11B and GFP, Sample 3 was human HSC transduced with lentivirus expressing FLAG-tagged mutant BCL11B and GFP
2016-07-29 | E-GEOD-84941 | biostudies-arrayexpress
Project description:The mouse Ikaros-deficient thymic lymphoma cell line T29 was transduced with an empty retrovirus (MigR1) or a retrovirus expressing an fusion proein between Ikaros1 and the ligand binding domain of the estrogen receptor. Cells trreated with ethanol or 4-hydroxy-tamoxyfen (4OHT) for 24h were profiled. We used expression of an inducible ersion of the Ikaros protein in an Ikaros-deficient cell line to identify Ikaros-regulated genes
2013-04-17 | E-GEOD-46088 | biostudies-arrayexpress
Project description:The mouse Ikaros-deficient thymic lymphoma cell line T29 was transduced with a retrovirus expressing an fusion protein between a dominant-negative form of Mastermind and the ligand binding domain of the estrogen receptor. Cells trreated with Ethanol or 4-hydroxy-tamoxyfen for 24h were profiled. We used expression of an inducible ersion of the dominant negative Mastermind protein in an Ikaros-deficient cell line to identify Notch-regulated genes
2013-04-17 | E-GEOD-46089 | biostudies-arrayexpress
Project description:We identified DNAPK as one of the major proteins that physically interact with Autoimmune regulator (Aire). To establish physiological significance of DNAPK in Aire-driven expression of PTA genes in MECs, we utilized BM-reconstituted SCID mice (which express non functional DNAPK in their MECs) and RAG1 null mouse as a control. MECs from these mutated/reconstituted mice were sorted by Flow cytomety and their expression profile was analyzed using Affymetrix chips. The analysis shows that Aire-dependent PTA genes are significantly underexpressed in reconstituted SCIDS vs. RAGs (Controls), suggesting the involvement of DNAPK in Aire-mediated gene expression. Keywords: gene mutation Since SCID mice lack mature thymocytes and as a result thymic stroma, we reconstituted these animals by BM transfer (IP injection into 2-4d pups) 6 hrs post-irradiation (200rad). Reconstituted thymi were analyzed 6-8w after transfer.
2010-10-16 | E-GEOD-24734 | biostudies-arrayexpress
Project description:The transcription factor FOXN1 is a master regulator of thymic epithelial cell development and function. Here we demonstrate that FOXN1 expression is differentially regulated during organogenesis and participates in multi-molecular nuclear condensates essential for the factor's transcriptional activity. FOXN1's C-terminal sequence regulates the diffusion velocity within these aggregates and modulates the binding to proximal gene regulatory regions. These dynamics are significantly altered in a patient's FOXN1 mutant modified in its C-terminal sequence. This mutant is transcriptionally inactive and acts as a dominant negative factor displacing wild-type FOXN1 from condensates and causing athymia and severe lymphopenia in heterozygotes. Expression of the mutated mouse ortholog, Foxn1, selectively impairs mouse thymic epithelial cell (TEC) differentiation, revealing a gene dose dependency for individual TEC subtypes. We have therefore identified the cause for a primary immunodeficiency disease and determined the mechanism by which this FOXN1 gain-of-function mutant mediates its dominant negative effect.
2021-10-29 | PXD025552 | Pride
Project description:The mouse Ikaros-deficient thymic lymphoma cell line T29 was treated with a gamma-secretase inhibitor or vehicle (DMSO) for 36h and subjected to transcriptome analysis.
2013-04-17 | GSE46095 | GEO
Project description:The mouse Ikaros-deficient thymic lymphoma cell line T29 was treated with a gamma-secretase inhibitor or vehicle (DMSO) for 36h and subjected to transcriptome analysis. 4 samples
2013-04-17 | E-GEOD-46095 | biostudies-arrayexpress