Transcriptome analysis of peritoneal lavage of mice infected with T. gondii
Differential gene expression in mice infected with distinct Toxoplasma strains.
Sex, Specimen part
View SamplesType 2 diabetes (T2D) is the most common form of diabetes in humans and is closely associated with dyslipidemia and obesity that magnifies the mortality and morbidity related to T2D. The TALLYHO/JngJ (TH) mouse is a polygenic model for T2D characterized by obesity, hyperinsulinemia, impaired glucose uptake and tolerance, hyperlipidemia, and hyperglycemia. To determine the genetic factors that contribute to these T2D related characteristics in TH mice, we interbred TH mice with C57BL/6J (B6) mice. The parental, F1, and F2 mice were phenotyped at 8, 12, 16, 20, and 24 weeks of age for 4-hour fasting plasma triglyceride, cholesterol, insulin, and glucose levels, as well as body weights. Fat pad and carcass weights were measured at 24 weeks after sacrificing the mice. The F2 mice were genotyped genome-wide for 68 markers. Of 393 genotyped F2 mice, 16 were chosen from the extremes of the triglyceride distribution (8 high and 8 low), and liver, pancreas, muscle and adipose tissue were measured for gene expression. Gene expression quantitative trait locus (eQTL) analysis aided in selection of candidates underlying hyperlipidemia, diabetes and obesity QTLs. We identified several genetic loci that affected quantitative variation in plasma lipid and glucose levels and obesity traits.
Genetic and genomic analysis of hyperlipidemia, obesity and diabetes using (C57BL/6J × TALLYHO/JngJ) F2 mice.
Specimen part
View SamplesDomestic chicken has been intensively studied because of its role as an efficient source of lean meat. However, commercial broilers resulting from genetic selection for rapid growth demonstrate detrimental traits, such as excess deposition of abdominal adipose tissue, metabolic disorders, and reduced reproduction. Therefore fast-growing broilers represent obese chickens compared to slow-growing egg layers (e.g, Leghorn) or wild strain of meat-type chickens (e.g., Fayoumi). Fayoumi chickens, originating from Egypt, represent a harder stain of chickens, which are more resistant to diseases. Leghorn chickens are the original breed of commercial U.S layers. Both lines were maintained highly inbred by Iowa State University poultry geneticists with an inbreeding coefficient higher than 0.95. Both Fayoumi and Leghorn demonstrated lean phenotype compared to broilers, and these three lines of chickens are genetically distant from each other.
Molecular and metabolic profiles suggest that increased lipid catabolism in adipose tissue contributes to leanness in domestic chickens.
Sex, Age, Specimen part
View SamplesThe immune system plays a pivotal role in susceptibility to and progression of a variety of diseases. Due to its strong genetic basis, heritable differences in immune function may contribute to differential disease susceptibility between individuals. Genetic reference populations, such as the BXD (C57BL/6J X DBA/2J) panel of recombinant inbred (RI) mouse strains, provide a unique model through which to integrate baseline phenotypes in healthy individuals with heritable risk for disease because of the ability to combine data collected from these populations across multiple studies and time. We performed basic immunophenotyping (e.g. percentage of circulating B and T lymphocytes and CD4+ and CD8+ T cell subpopulations) in peripheral blood of healthy mice from 41 BXD RI strains to define the phenotypic variation in this model system and to characterize the genetic architecture that unlerlies these traits. Significant QTL models that explained the majority (50-77%) of phenotypic variance were derived for each trait and for the T:B cell and CD4+:CD8+ ratios. Combining QTL mapping with spleen gene expression data uncovered two quantitative trait transcripts (QTTs), Ptprk and Acp1, that which are candidates for heritable differences in the relative abundance of helper and cytotoxic T cells. These data will be valuable in extracting genetic correlates of the immune system in the BXD panel. In addition, they will be a useful resource in prospective, phenotype-driven model selection to test hypotheses about differential disease or environmental susceptibility between individuals with baseline differences in the composition of the immune system.
Identifying genetic loci and spleen gene coexpression networks underlying immunophenotypes in BXD recombinant inbred mice.
Sex, Specimen part
View SamplesDomestic broiler chickens rapidly accumulate adipose tissue due to intensive genetic selection for rapid growth and are naturally hyperglycemic and insulin resistant, making them an attractive addition to the suite of rodent models used for studies of obesity and type 2 diabetes in humans. Furthermore, chicken adipose tissue is considered as poorly sensitive to insulin and lipolysis is under glucagon control. Excessive fat accumulation is also an economic and environmental concern for the broiler industry due to the loss of feed efficiency and excessive nitrogen wasting, as well as a negative trait for consumers who are increasingly conscious of dietary fat intake. Understanding the control of avian adipose tissue metabolism would both enhance the utility of chicken as a model organism for human obesity and insulin resistance and highlight new approaches to reduce fat deposition in commercial chickens.
Transcriptomic and metabolomic profiling of chicken adipose tissue in response to insulin neutralization and fasting.
Specimen part
View SamplesPiwi proteins and their associated piRNAs are essential in the germline where they repress transposition, regulate translation, and guide epigenetic programming. Little is known, however, about the molecular mechanisms through which Piwi proteins and piRNAs mediate these processes. Here, we show that an evolutionarily conserved Tudor and KH-domain containing protein, Tdrkh (a.k.a. Tdrd2), partners with Miwi and Miwi2 in mice via symmetrically dimethylated arginine residues in Miwi and Miwi2. Tdrkh is localized to pi-bodies and piP-bodies and is required for nuclear localization of Miwi2. Genetic deletion of Tdrkh arrests meiosis at the zygotene stage, demethylates Line1 DNA, and up-regulates Line1 transposition, but does not promote apoptosis. Furthermore, Tdrkh mutants have severely reduced levels of mature piRNAs. Specifically, in Tdrkh mutants, piRNAs accumulate as a distinct population of 5’U-containing 31-37nt RNA that largely complements the missing mature piRNAs. These results demonstrate that the primary piRNA biogenesis pathway involves 3à5’ processing of the 31-37nt intermediates and that Tdrkh is required for this final step of piRNA biogenesis. However, Tdrkh is not required for the secondary piRNA biogenesis pathway (i.e., the ping pong cycle). These results shed light on mechanisms underlying primary piRNA biogenesis, an area in which information is conspicuously absent. Overall design: Tdrkh-floxed mice were generated by the University of Connecticut Gene Targeting and Transgenic Facility. The targeting vector utilized C57Bl6 Tdrkh genome sequences from BAC clone RP23-263K17 (Chori BACPAC) and floxed exons 2-4 (the start codon is in exon 2) and was electroporated into D2 ES cells, a male hybrid C57Bl6/129SEV line. Clones that survived positive selection with G418 and negative selection with gancyclovir were expanded and screened by PCR with primers recognizing endogenous and exogenous (vector-derived) sequences. Positive clones were fused to CD-1 embryos, and germline transmission from resulting pups was confirmed by test crosses to CD-1 mice (which also confirmed that all gametes were derived from the targeted clones). Positive animals were bred to FLP mice to delete the neomycin-targeting cassette, resulting in Tdrkh cKO mice on a C57Bl6/129 background. cKO mice were bred with EIIa-Cre transgenic mice to excise the floxed exons 2-4 and generate Tdrkh +/- animals. Heterozygous animas were intercrossed to remove the EIIA transgene. Two independent knockout lines were generated from independent cKO founder lines and showed identical phenotypes in all experiments performed.
Tdrkh is essential for spermatogenesis and participates in primary piRNA biogenesis in the germline.
Specimen part, Subject
View SamplesTo investigate the transcriptional remodelling during EMT, we treated normal murine mammary gland epithelial cells with TGFbeta for 0, 2h, 6h, 12h, 24h, 36h, 48h, 60h, 72h, 96h, 168h and 240h. Using WGCNA and pathway enrichment analysis we identified multiple gene expression modules that were enriched in general, signaling, metabolic or stuctural pathways highly relevant for EMT. Overall design: RNA sequencing of NMuMG/E9 cells induced to undergo EMT by treatment with TGFbeta from 0-10 days.
PyMT-1099, a versatile murine cell model for EMT in breast cancer.
Specimen part, Cell line, Subject
View SamplesWe provide data showing alternative splicing regulation by Muscleblind proteins in MEFs. MEFs lacking functional Muscleblind (DKO MEFs) were stably reconstituted with Muscleblind proteins from Homo sapiens, Ciona intestinalis, Drosophila melanogaster, Caenorhabditis elegans or Trichoplax adhaerens and splicing regulation was explored using RNA-seq analysis followed by MISO (Mixture of Isoforms). Overall design: Alternative splicing was accessed using RNA-sequencing data from five DKO MEF lines reconstituted with different GFP-tagged Muscleblind homologs or GFP alone and compared to RNA-seq data from three WT MEF lines and three control DKO MEFs (no Muscleblind reconstitution). A total of 12 samples were used for high-throughput sequencing.
Conservation of context-dependent splicing activity in distant Muscleblind homologs.
Subject
View SamplesTo identify the potential ovarian cancer stem cell gene expression profile from isolated side population of fresh ascites obtained from women with high-grade advanced stage papillary serous ovarian adenocarcinoma
Identification of a potential ovarian cancer stem cell gene expression profile from advanced stage papillary serous ovarian cancer.
Specimen part
View SamplesTo define H3K27me3 modified genes in intestinal stem, progenitor and epithelial cells, we performed chromatin immunoprecipitation coupled with high-throughput sequencing (ChIP-Seq). We used RNA-sequencing to profile gene expression changes during intestinal stem cell differentiation into mature villus cells, as well as genes perturbed upon loss of PRC2 activity (deletion of Eed) . We find thousands of genes that change in expression including many H3K27me3 marked genes. The deregulated genes reaveal a intestinal tissue specific role of PRC2. Overall design: H3K27me3, H3K4me2 and RNA Pol2 ChIP-Seq analysis of isolated mouse intestinal stem cells, enterocyte and secretory progenitor cells, and mature villus cells. RNA seq analysis of control mouse villus cells, control intestinal stem cells and Eed-deleted villus.
Acquired Tissue-Specific Promoter Bivalency Is a Basis for PRC2 Necessity in Adult Cells.
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