Purpose: To investigate the gene regulatory networks during photoreceptor differentiation.
Targeting of GFP to newborn rods by Nrl promoter and temporal expression profiling of flow-sorted photoreceptors.
No sample metadata fields
View SamplesMurine models have been valuable instruments in defining the pathogenesis of diabetic nephropathy (DN), but they only partially recapitulate disease manifestations of human DN, limiting their utility . In order to define the molecular similarities and differences between human and murine DN, we performed a cross-species comparison of glomerular transcriptional networks. Glomerular gene expression was profiled in patients with early type 2 DN and in three mouse models (streptozotocin DBA/2 mice, db/db C57BLKS, and eNOS-deficient C57BLKS db/db mice). Species-specific transcriptional networks were generated and compared with a novel network-matching algorithm. Three shared, human-mouse cross-species glomerular transcriptional networks containing 143 (Human-STZ), 97 (Human- db/db), and 162 (Human- eNOS-/- db/db) gene nodes were generated. Shared nodes across all networks reflected established pathogenic mechanisms of diabetic complications, such as elements of JAK-STAT and VEGFR signaling pathways . In addition, novel pathways not formally associated with DN and cross-species gene nodes and pathways unique to each of the human-mouse networks were discovered. The human-mouse shared glomerular transcriptional networks will assist DN researchers in the selection of mouse models most relevant to the human disease process of interest. Moreover, they will allow identification of new pathways shared between mice and humans.
Identification of cross-species shared transcriptional networks of diabetic nephropathy in human and mouse glomeruli.
Age, Specimen part, Disease, Disease stage, Treatment
View SamplesThe glucocorticoid receptor overexpression in early life is sufficient to alter gene expression patterns for the rest of the animal's life.
Early-life forebrain glucocorticoid receptor overexpression increases anxiety behavior and cocaine sensitization.
Sex, Specimen part
View SamplesGenetic loci displaying environmentally responsive epigenetic marks, termed metastable epialleles, offer a solution to the paradox presented by genetically identical yet phenotypically distinct individuals. The murine viable yellow agouti (Avy) locus is a well-described metastable epiallele that serves as a visual epigenetic biosensor. The Avy locus exhibits a high R-value or ratio of inter-individual (Vi) to inter-tissue (Vt) variance in gene expression, characteristic of what we term the Agouti Expression Fingerprint. We propose a novel method for identification of candidate metastable epialleles based on the Agouti Expression Fingerprint, defining candidates as loci with R-values greater than 1.5 on expression microarray.
No associated publication
Sex
View SamplesThe mechanisms of diabetic neuropathy (DN) development and progression are not fully understood. We examined global gene expression in the sciatic nerve (SCN) of BKS-db/db mice at 8 and 24 weeks of age to identify genetic pathways altered in peripheral nerves at early and advanced stages of DN. The sets of differentially expressed genes were analyzed to identify enriched biological functions and regulated genetic pathways. Our results suggest that carbohydrate metabolism and lipid metabolism pathways are dysregulated in the db/db SCN at 8 weeks of age. Impairment of Schwann cell-extracellular matrix interaction and axon guidance occurs early in the development of DN, while neurotrophic support, neurotransmitter transport and axonogenesis are impaired at the advanced stage of DN. Gene expression changes also suggest that oxidative stress- and inflammation-mediated nerve damage occurs by 8 weeks.
No associated publication
Age, Specimen part
View SamplesStarting with our early global expression analyses of TCDD-treated human hepatoma cells {Puga, 2000 4679 /id}, the AHR transcriptional induction profile has been extensively studied, whether activated by TCDD, B[a]P or in the absence of exogenous ligands (reviewed in {Frericks, 2007 5618 /id}). In addition to using prior knowledge to integrate expression profiles into the AHR gene target network, we performed a new set of expression profile analyses of wild type Hepa-1c1c7 and c35 cell lines and compared the responses in nave cells with responses in TCDD or B[a]P exposed cells for 8 hours. Results of our expression array studies are in close agreement with current knowledge.
No associated publication
Sex, Specimen part, Cell line
View SamplesGlomerular RNA comparison between wild-type and podocyte specific deletion of the PTIP gene in 1 month old kidneys. The PTIP gene was deleted using a floxed allele and a Podocin-Cre driver strain.
Altering a histone H3K4 methylation pathway in glomerular podocytes promotes a chronic disease phenotype.
Specimen part
View SamplesPhotoreceptor damage in adult mammals results in permanent cell loss and glial scarring in the retina. In contrast, adult zebrafish can regenerate photoreceptors following injury. By using a stable transgenic line in which GFP is driven by the cis-regulatory sequences of a glial specific marker gfap, Tg(gfap:GFP)mi2002, previous studies showed that Mller glia, the radial glial cells in the retina, proliferate after photoreceptor loss and give rise to neuronal progenitors that eventually differentiate into regenerated photoreceptors. To identify the molecular mechanisms that initiate this regenerative response, Mller glia were isolated from Tg(gfap:GFP)mi2002 fish during the early stages of regeneration after light lesion and gene expression profiles were generated by microarray analyses.
Genetic evidence for shared mechanisms of epimorphic regeneration in zebrafish.
No sample metadata fields
View SamplesTo study the possible fibrotic role of FIZZ2, bleomycin was used to induce pulmonary fibrosis in wild type and FIZZZ2 knockout mice, lungs were then harvested and processed for RNA isolation.
FIZZ2/RELM-β induction and role in pulmonary fibrosis.
Specimen part
View SamplesIre1 conditional null or control mice of 3-months old were injected intraperitoneally with TM or vehicle.
The unfolded protein response transducer IRE1α prevents ER stress-induced hepatic steatosis.
Specimen part
View Samples