Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Gene profiling of mouse brain infected with scrapie strain 22A_End-point analysis

ABSTRACT: This SuperSeries is composed of the following subset Series: GSE12321: Brain_22A-Scrapie_End-point_PR04-39-to-46_using_GPL7118 GSE12322: Brain_22A-Scrapie_End-point_PR06-11-to-14_using_GPL7121 Refer to individual Series

ORGANISM(S): Mus musculus

SUBMITTER: Reuben Saba

PROVIDER: E-GEOD-12354 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

A miRNA signature of prion induced neurodegeneration.

Saba Reuben R Goodman Chelsey D CD Huzarewich Rhiannon L C H RL Robertson Catherine C Booth Stephanie A SA

PloS one 20081106 11

MicroRNAs (miRNAs) are small, non-coding RNA molecules which are emerging as key regulators of numerous cellular processes. Compelling evidence links miRNAs to the control of neuronal development and differentiation, however, little is known about their role in neurodegeneration. We used microarrays and RT-PCR to profile miRNA expression changes in the brains of mice infected with mouse-adapted scrapie. We determined 15 miRNAs were de-regulated during the disease processes; miR-342-3p, miR-320, ...[more]

PMID: 18987751

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Project description:Over-expression of wild type PrP in skeletal muscles is sufficient to cause a primary myopathy with no signs of peripheral neuropathy, possibly due to accumulation of a cytotoxic truncated form of PrP and/or PrP aggregation. In this study we used DNA microarrays to identify 1499 transcripts that are temporally deregulated concomitant with inducible PrPC over-expression in the skeletal muscles of transgenic mice. Examination using microarrays revealed a transcriptional profile with both similarities and differences to previously investigated models of myopathies. Down-regulation of genes coding for the myofibrillar proteins MYH2, MYH6, MYH7, MYL2, MYL3 and up-regulation of lysosomal genes CTSS, CTSD, CTSZ, DPEP2, HEXA, HEXB and LAMP1 coincide with the observed myopathy and lysosome accumulation on over-expression of PrPC. Down-regulation of the MEF2C gene, a key regulatory transcriptional factor muscle development and remodeling of adult muscles in response to physiologic and pathologic signals, may contribute to the centrally placed nuclei in the skeletal muscles. Significantly, up-regulation of genes involved in p53 signaling and the induction of p53 protein, suggest a central role for this molecule in the myopathy. Several p53-regulated genes involved in cell cycle arrest (CDNK1A, GADD45a and GADD45b) and apoptosis (BAK1, PMAIP1, BBC3, and BAX) are induced. We suggest that PrPC over-expression in skeletal muscles, possibly in response to accumulation of a cytotoxic truncated form of PrP, causes a primary myopathy involving the induction of p53-dependent pathways. Wild type (WT), PrP-null (KO), and Tg(HQK) mice were fed food pellets either lacking or containing 6g doxycycline (Dox)/kg food to induce PrPC expression. Skeletal muscles from the quadriceps of hind legs were removed at day 0, 4, 7, 14, 30 and 60 days following administration of Dox. Total RNA was isolated from these tissues for use in subsequent microarray analysis. Mouse gene expression was analysed by two-colour microarray experiments using an inhouse manufactured 16K mouse cDNA microarray. Age matched reference mice (WT) and experimental (KO and HQK) Alexa Flour labeled aRNA were used in each competitive hybridization. Each sample was labeled individually with both Alexa Fluor 555 and 647 for subsequent dye-swapped hybridizations to account for intensity bias. 3 individual mice from each experimental group at each time point were individually processed for separate microarrays. We used the program EDGE to identify genes that were differentially expressed in mouse skeletal muscle in either transgenic HQK mice over expressing PrP, or PrP knock out (KO) mice after administration of Dox. We used a P value cut-off of 0.05 as the criteria of selection of significantly differentially expressed genes.

Dataset Information

Gene profiling of mouse brain infected with scrapie strain 22A_End-point analysis

Publications

A miRNA signature of prion induced neurodegeneration.

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