Hair cells (HCs) are the mechanoreceptors responsible for hearing and balance in the inner ear. Multiple factors cause HC loss including aging, noise exposure and genetic predisposition. A barrier to hearing restoration after HC loss is the inability of mammalian auditory HCs to spontaneously regenerate. Multiple factors are shown to be crucial for HC development and represent good candidates for regenerative studies. Atoh1 is widely accepted to be necessary and contextually sufficient for driving HC fate. Furthermore, the miRNA-183 family is known to be expressed at the time of HC differentiation, and mutations in miR-96 (one member of the family) can cause deafness both in mouse and human.
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Specimen part
View SamplesB cell chronic lymphocytic leukemia (CLL) is often preceded by a benign monoclonal or oligoclonal CD5+ B cell lymphocytosis. We have generated transgenic mice expressing a catalytically inactive, dominant-negative recombination activating gene 1 (dnRAG1 mice) in the periphery. These animals develop an early-onset indolent CD5+ B cell lymphocytosis, caused in part by a defect in secondary V(D)J rearrangements initiated to alter autoreactive B cell receptor specificity. Hypothesizing that the CD5+ B cells accumulating in dnRAG1 mice represent a CLL precursor, we crossed dnRAG1 mice with CLL-prone E-TCL1 mice to determine whether dnRAG1 expression in E-TCL1 mice accelerates the onset of CLL-like disease. We find that CD5+ B cell expansion and CLL progression occurs more rapidly and uniformly in double-transgenic mice (DTG mice) compared to E-TCL1 mice, but with similar phenotypic and leukemogenic features. To gain insight into genes or pathways responsible for CD5+ B cell accumulation in the transgenic mice, we performed comparative gene expression profiling studies using normal and CD5+ B cells isolated from wild-type and transgenic mice at either 12 weeks of age (pre-leukemia) or at CLL onset in DTG mice (using age-matched wild-type and single-transgenic mice as controls). These analyses confirm the upregulation of tolerogenic genes in CD5+ B cells and reveal a possible role for prolactin signaling in the regulation of receptor editing. This study suggests that a failure to remodel B cell antigen receptor genes in response to autoreactivity may promote the benign accumulation of CD5+ B cells, which may then be subjected to secondary genetic lesions that promote CLL progression.
Accelerated progression of chronic lymphocytic leukemia in Eμ-TCL1 mice expressing catalytically inactive RAG1.
Age, Specimen part
View SamplesTransgenic FVB/NCrl-Tg(GFAP-Mir183,Mir96,Mir182)MDW1 mice (Tg1MDW) overexpress this neurosensory-specific miRNA cluster in the inner ear and were developed as a model system to identify target genes and biologic processes regulated by the miR-183 cluster.
A mouse model of miR-96, miR-182 and miR-183 misexpression implicates miRNAs in cochlear cell fate and homeostasis.
Specimen part
View SamplesCre recombinase-mediated conditional knockout of floxed Dicer1 alleles causes depletion of small RNAs including microRNAs, which function to repress target mRNA expression by inhibiting translation and/or stimulating mRNA degradation.
MicroRNA-183 family expression in hair cell development and requirement of microRNAs for hair cell maintenance and survival.
Specimen part
View SamplesTranscriptome analysis of P16 cochlea from wild type and miR-183/96 Knock out mice
No associated publication
Specimen part
View SamplesThe transcriptome is the complete set of all RNA transcripts produced by the genome in a cell and reflects the genes that are being actively expressed. Transcriptome analysis is essential for understanding the genetic mechanism controlling the phenotype of a cell.
Characterization of transcriptomes of cochlear inner and outer hair cells.
Specimen part
View SamplesB cells produce important cytokines regulate bone metabolism. We comparison gene expression patterns of circulating B cells in blood from 20 postmenopausal female smokers with low or high bone mineral density (BMD): 10 low BMD vs. 10 high BMD.
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View SamplesB cells produce important cytokines regulate bone metabolism. We comparison gene expression patterns of circulating B cells in blood from 20 postmenopausal females with low or high bone mineral density (BMD): 10 low BMD vs. 10 high BMD.
No associated publication
No sample metadata fields
View SamplesExposure to ultraviolet (UV) irradiation is the major cause of nonmelanoma skin cancer, the most common form of cancer in the United States. UV irradiation has a variety of effects on the skin associated with carcinogenesis, including DNA damage and effects on signal transduction. The alterations in signaling caused by UV regulate inflammation, cell proliferation, and apoptosis. UV also activates the orphan receptor tyrosine kinase and proto-oncogene Erbb2 (HER2/neu). In this study, we demonstrate that the UV-induced activation of Erbb2 regulates the response of the skin to UV. Inhibition or knockdown of Erbb2 before UV irradiation suppressed cell proliferation, cell survival, and inflammation after UV. In addition, Erbb2 was necessary for the UV-induced expression of numerous proinflammatory genes that are regulated by the transcription factors nuclear factor-kappaB and Comp1, including interleukin-1beta, prostaglandin-endoperoxidase synthase 2 (Cyclooxygenase-2), and multiple chemokines. These results reveal the influence of Erbb2 on the UV response and suggest a role for Erbb2 in UV-induced pathologies such as skin cancer.
Erbb2 regulates inflammation and proliferation in the skin after ultraviolet irradiation.
No sample metadata fields
View SamplesThe purpose of this study was to characterize the transcriptional effects induced by subcutaneous IFN-beta-1b treatment (Betaferon, 250 g every other day) in patients with relapsing-remitting form of multiple sclerosis (MS).
Long-term genome-wide blood RNA expression profiles yield novel molecular response candidates for IFN-beta-1b treatment in relapsing remitting MS.
Sex
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