Objective Previous studies showed that genetic deletion or pharmacological blockade of the Receptor for Advanced Glycation Endproducts (RAGE) prevents the early structural changes in the glomerulus associated with diabetic nephropathy (DN). To overcome limitations of mouse models that lack the progressive glomerulosclerosis observed in humans, we studied the contribution of RAGE to DN in the OVE26 type 1 mouse, a model of progressive glomerulosclerosis and decline of renal function.
Deletion of the receptor for advanced glycation end products reduces glomerulosclerosis and preserves renal function in the diabetic OVE26 mouse.
Sex, Age, Specimen part, Disease, Disease stage
View SamplesPreviously we have shown significant differences in lactation performance, mammary gland histology and expression profiles of mammary transcriptome during peak-lactation (lactation day 9; L9) between the ordinary CBA/CaH (CBA) and the superior QSi5 strains of mice. In the present study, we compared mammary gland histology between CBA and QSi5 at mid-pregnancy (pregnancy day 12; P12). We assessed lactation performance during the first 8 days of lactation of the 13th - 14th generation of the Advanced Intercross Line (AIL) (CBA X QSi5) mice.
Identification of gene sets and pathways associated with lactation performance in mice.
Specimen part
View SamplesIncreasing evidence suggests that Long non-coding RNAs (LncRNAs) represent a new class of regulators of stem cells. However, the roles of LncRNAs in stem cell maintenance and myogenesis remain largely unexamined. For this study, hundreds of novel intergenic LncRNAs were identified that are expressed in myoblasts and regulated during differentiation. One of these LncRNAs, termed LncMyoD, is encoded next to the Myod gene and is directly activated by MyoD during myoblast differentiation. Knockdown of LncMyoD strongly inhibits terminal muscle differentiation largely due to a failure to exit the cell cycle. LncMyoD directly binds to IGF2-mRNA-binding-protein 2 (IMP2) and negatively regulates IMP2-mediated translation of proliferation genes such as N-Ras and c-Myc. While the RNA sequence of LncMyoD is not well-conserved between human and mouse, its locus, gene structure and function is preserved. The MyoD-LncMyoD-IMP2 pathway elucidates a mechanism as to how MyoD blocks proliferation to create a permissive state for differentiation.
A long non-coding RNA, LncMyoD, regulates skeletal muscle differentiation by blocking IMP2-mediated mRNA translation.
Age
View SamplesThe QSi5 inbred strain of mice was established from an outbred Quackenbush-Swiss strain by full-sib inbreeding and selection on the basis of increased litter size and shortened inter-litter interval in the Department of Veterinary Physiology (later REPROGEN) , University of Sydney (Holt et al., 2004). The strain has an average litter size of more than 13 pups, and females commonly nurse up to 18 pups with greater than 90% survival to weaning. Along with an increased body weight (BW), these traits are clearly indicative of enhanced lactation performance (Knight et al., 1986). Indeed lactation performance, assessed by a weigh-suckle-weigh method, was 3-fold greater in QSi5 mice than the CBA strain (Riley et al., 2006). In this study, we utilize the divergent phenotypes of QSi5 and CBA/CaH mice to identify genes associated with enhanced mammary gland capacity.
Transcriptome analysis identifies pathways associated with enhanced maternal performance in QSi5 mice.
No sample metadata fields
View SamplesTo model the potential diabetogenic effects of higher level of HSD11B1 in b-cells of the pancreas in vivo, we created a transgenic model overexpressing HSD11B1 under the mouse insulin I promoter (MIP-HSD1) in diabetes-prone C57Bl/KsJ mice. KsJ wild type and MIP-HSD1 heterozygous mice have been high fat fed for 12 weeks. Pancreata have been perfused with collagenase and islets isolated by hand picking. Isolated islets (around 500) coming from at least 3 mice (around 200/mice) have been directly lysed in Trizol. Total RNA have been extracted by Trizol plus RNA Purification Kit (invitrogen).
Optimal elevation of β-cell 11β-hydroxysteroid dehydrogenase type 1 is a compensatory mechanism that prevents high-fat diet-induced β-cell failure.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Sequentially acting Sox transcription factors in neural lineage development.
Specimen part
View SamplesWe report sequential binding but unique functions of different Sox transcription factors during distinct stages of neural differentiation
Sequentially acting Sox transcription factors in neural lineage development.
Specimen part
View SamplesContinuous regeneration of digestive enzyme (zymogen) secreting chief cells is a normal aspect of stomach function that is disrupted in pre-cancerous lesions. Regulation of zymogenic cell (ZC) differentiation is poorly understood. Here we profile Parietal, Pit, and Zymogenic cells for comparison and study.
The maturation of mucus-secreting gastric epithelial progenitors into digestive-enzyme secreting zymogenic cells requires Mist1.
Specimen part
View SamplesPolyinosinic:polycytidylic acid (poly I:C) is a synthetic analogue of double-stranded (ds)RNA, a molecular pattern associated with viral infections, that is used to exacerbate inflammation in lung injury models. Despite its frequent use, there are no detailed studies of the responses elicited by a single topical administration of poly I:C to the lungs of mice. Our data provides the first demonstration that the molecular responses in the airways induced by poly I:C correlate to those observed in the lungs of COPD patients. These expression data also revealed three distinct phases of response to poly I:C, consistent with the changing inflammatory cell infiltrate in the airways. Poly I:C induced increased numbers of neutrophils and NK cells in the airways, which were blocked by CXCR2 and CCR5 antagonists, respectively. Using gene set variation analysis on representative data sets, gene sets defined by poly I:C-induced DEGs were enriched in the molecular profiles of chronic obstructive pulmonary disease (COPD), but not idiopathic pulmonary fibrosis patients. Collectively, these data represent a new approach for validating the clinical relevance of preclinical animal models and demonstrate that a dual CXCR2/CCR5 antagonist may be an effective treatment for COPD patients.
Double-stranded RNA induces molecular and inflammatory signatures that are directly relevant to COPD.
Sex, Specimen part, Time
View SamplesAtherosclerosis is a chronic inflammatory disease characterized by the accumulation of lipid-loaded macrophages in the arterial wall. Intimal macrophages internalize modified lipoproteins such as oxidized LDL (oxLDL) through scavenger receptors, leading to storage of excess cholesteryl esters in lipid bodies and a "foam cell" phenotype. In addition, stimulation of macrophage Toll-like receptors (TLRs) has been shown to promote lipid body proliferation. We investigated the possibility that there are transcriptional regulators that are common to both pathways for stimulating foam cell formation (modified lipoproteins and TLR stimulation), and identified the transcription factor ATF3 as a candidate regulator.
ATF3 protects against atherosclerosis by suppressing 25-hydroxycholesterol-induced lipid body formation.
Sex, Specimen part
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