Unknown,Transcriptomics,Genomics,Proteomics

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Transcription profiling of Paneth cells from Atg16l1hm mice with CR6 virus

ABSTRACT: Transcription profiling of Paneth cells from Atg16l1hm mice with CR6 virus

ORGANISM(S): Mus musculus

SUBMITTER: Chad Storer

PROVIDER: E-TABM-957 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:Background: We have previously used the rat 4 day Complete Freund's Adjuvant (CFA) model to screen compounds with potential to reduce osteoarthritic pain. The aim of this study was to identify genes altered in this model of osteoarthritic pain and use this information to infer analgesic potential of compounds based on their own gene expression profiles using the Connectivity Map approach. Results: Using microarrays, we identified differentially expressed genes in L4 and L5 dorsal root ganglia (DRG) from rats that had received intraplantar CFA for 4 days compared to matched, untreated control animals. Analysis of these data indicated that the two groups were distinguishable by differences in genes important in immune responses, nerve growth and regeneration. This list of differentially expressed genes defined a âCFA signatureâ. We used the Connectivity Map approach to identify pharmacologic agents in the Broad Institute Build02 database that had gene expression signatures that were inversely related (ânegatively connectedâ) with our CFA signature. To test the predictive nature of the Connectivity Map methodology, we tested phenoxybenzamine (an alpha adrenergic receptor antagonist) â one of the most negatively connected compounds identified in this database - for analgesic activity in the CFA model. Our results indicate that at 10mg/kg, phenoxybenzamine demonstrated analgesia comparable to that of Naproxen in this model. Conclusion: Evaluation of phenoxybenzamine-induced analgesia in the current study lends support to the utility of the Connectivity Map approach for identifying compounds with analgesic properties in the CFA model. A naive (control) group of rats (n = 6) and a group of rats injected with CFA (n = 6) were used for gene expression profiling experiments. One animal from the control group did not yield sufficient amount of RNA for microarray and thus was omitted from further processing. In total, 5 microarrays each from the 5 animals in the control group, and 6 microarrays each from the 6 animals in the CFA group were analyzed.

Project description:Members of the Nuclear mRNA Export Factor (NXF) family are implicated in nuclear export and/or cytoplasmic transport of mRNAs in eukaryotic cells. We previously proposed NXF5 to be involved in cognitive development and aimed to study its functional role further using a mouse model. The syntenic region of the human Xcen-GLA-NXF5-NXF2-NXF3-BEX4-Xqter in the mouse is Xcen-Gla-Nxf2-Nxf7-Nxf3-Bex4-Xqter strongly indicating that mouse Nxf2 is the homolog of human NXF5. However, our functional analyses demonstrated that mouse Nxf7 is actually the functional homolog of NXF5. Both orthologs are expressed in brain, although at low levels, show predominant cytoplasmic localization, and present a granular staining in neuronal dendrites, all indicative for a role in cytoplasmic mRNA transport or metabolism. The mouse and human Nxf2/NXF2 proteins on the other hand, show highest expression in testis, and mostly nuclear staining with incorporation in the nuclear membrane, suggesting a predominant role in nuclear mRNA export. Based on these findings we generated an Nxf7 knockout mouse, which was viable and fertile and no gross anatomical changes or morphological brain abnormalities were detected. Detailed behavioral analysis demonstrated that Nxf7 KO mice displayed a deficit in hippocampus-dependent spatial learning and memory. At the cellular level, this was accompanied by impaired hippocampal long-term potentiation, but normal long-term depression, suggesting a severe functional imbalance in NMDA-dependent synaptic plasticity. In conclusion, the present findings indicate that NXF5, and its murine ortholog Nxf7, play a crucial role in neurocognitive (memory) functions, and explain why its deletion leads to intellectual disability. Two male wild type (WT1 and WT2) and two Nxf7 knockout (KO1 and KO2) mice were used in each hybridization experiment (hippocampus or cortex). A loop-design hybridization scheme (WT1/KO1, KO1/WT2, WT2/KO2 and KO2/WT1) was performed for each experiment so as to have each sample labeled once with Cy5 and once with Cy3, and hybridised to both samples of the other genotype (WT or KO). Hybridization was done on Agilent Mouse Whole Genome arrays according to the manufacturerM-bM-^@M-^Ys procedures.

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Transcription profiling of Paneth cells from Atg16l1hm mice with CR6 virus

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