Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA172114 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:miR-146a is a NF-κB induced microRNA that serves as a feedback regulator of this critical pathway. In mice, deficiency of miR-146a results in hematolymphoid cancer at advanced ages as a consequence of constitutive NF-κB activity. In this study, we queried whether the deficiency of miR-146a contributes to B-cell oncogenesis. Combining miR-146a deficiency with transgenic expression of c-Myc led to the development of highly aggressive B-cell malignancies. Mice transgenic for c-Myc and deficient for miR-146a were characterized by significantly shortened survival, increased lymph node involvement, differential involvement of the spleen and a mature B-cell phenotype. High-throughput sequencing of the tumors revealed significant dysregulation of approximately 250 genes. Amongst these, the transcription factor Egr1 was consistently upregulated in mice deficient for miR-146a. Interestingly, transcriptional targets of Egr1 were enriched in both the high-throughput dataset and in a larger set of miR-146a-deficient tumors. miR-146a overexpression led to downregulation of Egr1 and downstream targets with concomitant decrease in cell growth. Direct targeting of the human EGR1 by miR-146a was seen by luciferase assay. Together our findings illuminate a bona fide role for miR-146a in the modulation of B-cell oncogenesis and reveal the importance of understanding microRNA function in a cell- and disease-specific context.
2016-03-20 | GSE67113 | GEO
Project description:Purpose: To find out the global transcriptomic change induced by overexpression of miR-146a in thymus Methods:Thymic mRNA profile of two pools from age (five to six-week old)- and gender (one male and one female for each pool)- matched wild-type (WT) and miR-146a transgenic (Tg) mice were generated by deep sequencing using Illumina HiSeq 2500. The clean reads that passed quality filters were mapped against Mus musculus genome using HotHap2, and the only uniquely mapped reads were used to calculate reads per kilobase of exon per million fragment (RPKM) values for each sample. The transcript isoform with a fold-change over 2 and q<0.001 were considered differentially expressed. Conclusion: Our study identified 101 differently expressed transcripts in thymus from miR-146a Tg mice, including 56 down-regulated transcripts covering 49 genes which are the candidate targets of miR-146a
2018-02-14 | GSE99428 | GEO
Project description:MiR-146a is an important regulator of innate inflammatory responses and is also implicated in cell death and survival. Here, we identified microglia as the main cellular source of miR-146a among mouse CNS resident cells. We further characterized the phenotype of miR-146a KO microglia cells during in vivo demyelination induced by cuprizone (CPZ) and found reduced number of CD11c+ microglia in the KO compared to WT mice. Microglia were also isolated from the brain, and the proteome was analyzed by liquid chromatography mass spectrometry.
2020-06-29 | PXD015939 | Pride
Project description:miR-146a acts as a negative feedback regulator of inflammation. To investigate the role of miR-146a in psoriasis psoriasiform skin inflammation was indeuced in Mir-146a-/- and wild type mice (C57BL6J) by topical applciation of imiquimod (IMQ)-cream (Aldara). Gene expression profiling (Affymetrix) was used to identify transcriptomic changes associated with psoriasis-like skin inflammation in wild type vs. miR-146a -/-mice.
2016-02-19 | GSE78057 | GEO
Project description:A long-prevailing model has held that the “seed” region (nucleotides 2-8) of a microRNA is typically sufficient to mediate target recognition and repression. However, numerous recent studies, both within the context of defining miRNA/target pairs by direct physical association and by directly assessing this model in vivo in C. elegans have brought this model into question. To test the importance of miRNA 3' pairing in vivo, in a mammalian system, we engineered a mutant murine mir-146a allele in which the 5' half of the mature microRNA retains the sequence of the wild-type mir-146a but the 3ʹ half has been altered to be anti-complementary to the wild-type miR-146a sequence. Mice homozygous or hemizygous for this mutant allele are phenotypically indistinguishable from wild-type controls and do not recapitulate any of the immunopathology previously described for mir-146a-null mice. Our results strongly support the conclusion that 3ʹ pairing is dispensable in the context of the function of a key mammalian microRNA.
2019-02-09 | PXD011413 | Pride
Project description:This study set out to examine CD4 T cell differentiation in a mouse model of diabetes based on transgenic expression of ovalbumin under the control of the rat insulin promoter and co-expression of the DO11.10 transgene (DO11 x rip-mOVA mice). The transcriptome of T cells isolated from the pancreatic lymph nodes (lymph nodes draining the site of self antigen expression) was compared with that of T cells isolated from inguinal lymph nodes (non-draining lymph nodes). T cells were sorted based on expression of CD4, DO11.10 TCR (KJ-126), CD25 and CD69.
2014-10-07 | GSE62104 | GEO
Project description:This study set out to examine CD4 T cell differentiation in a mouse model of diabetes based on transgenic expression of ovalbumin under the control of the rat insulin promoter and co-expression of the DO11.10 transgene (DO11 x rip-mOVA mice). The transcriptome of T cells isolated from the pancreatic lymph nodes (lymph nodes draining the site of self antigen expression) was compared with that of T cells isolated from inguinal lymph nodes (non-draining lymph nodes). T cells were sorted based on expression of CD4, DO11.10 TCR (KJ-126), CD25 and CD69. Primary cells from 6 week old DO11 x rip-mOVA mice were isolated ex-vivo from the pancreatic lymph nodes or inguinal lymph nodes. Cells were sorted by flow cytometry using antibodies to CD4, DO11.10 TCR (KJ-126+), CD25 and CD69. 3-6 replicates were collected per experimental group with each replicate deriving from 14 mice. RNA was isolated using the RNeasy micro kit (Qiagen).
2014-10-07 | E-GEOD-62104 | biostudies-arrayexpress
Project description:To determine the influence of primary tumors on pre-metastatic lymph nodes, we have employed whole genome microarray expression profiling as a discovery platform to identify gene signatures of B cells from tumor-draining lymph nodes, compared with normal lymph nodes. We subcutaneously inoculated C57BL/6 mice with the 4T1 mammary carcinoma. Two weeks later, tumor-draining lymph nodes were dissociated and B cells (CD19+) were sorted. Lymph nodes B cells from normal mice without tumor bearing were set as controls.
2018-04-18 | GSE113250 | GEO
Project description:To determine the influence of primary tumors on pre-metastatic lymph nodes, we have employed whole genome microarray expression profiling as a discovery platform to identify gene signatures of stromal cells from tumor-draining lymph nodes, compared with normal lymph nodes. We subcutaneously inoculated C57BL/6 mice with the 4T1 mammary carcinoma. Two weeks later, tumor-draining lymph nodes were dissociated and stromal cells (CD45-) were sorted. Lymph nodes stromal cells from normal mice without tumor bearing were set as controls.
2018-04-18 | GSE113249 | GEO
Project description:miR-146a acts as a negative feedback regulator of inflammation. To investigate the role of miR-146a in psoriasis psoriasiform skin inflammation was indeuced in Mir-146a-/- and wild type mice (C57BL6J) by topical applciation of imiquimod (IMQ)-cream (Aldara). Gene expression profiling (Affymetrix) was used to identify transcriptomic changes associated with psoriasis-like skin inflammation in wild type vs. miR-146a -/-mice. A daily topical dose of 31.25 mg of Aldara cream (5% IMQ) was applied on the right ear of miR-146a -/- and C57BL/6 mice on three consecutive days to induce psorisis-like skin inflammation. Mice were sacrificed at day 4. Ear flaps were collected for total RNA extraction and hybridization on Affymatrix GeneTitan plate format Gene ST 2.1 (mouse).
2016-02-19 | E-GEOD-78057 | biostudies-arrayexpress