Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Aberrant brain miRNA target and miRISC gene expression in the anx/anx anorexia mouse model

ABSTRACT: The anorexia mouse model, anx/anx, carries a spontaneous mutation not yet identified and homozygous mutants are characterized by anorexia-cachexia, growth failure and abnormal behavior, such as head weaving, hyperactivity, and ataxia. In order to test if miRNA machinery could influence the phenotype of these mice, RNA samples from mutant and wild type hypothalamus and cortex were hybridized to microarray chips based on LNA probes allowing the detection of 279 mouse miRNAs and to Agilent 44k chips to analyze the whole mRNA transcriptome. In anx/anx hypothalamus we found that predicted miRNA targets were preferentially upregulated in a lineally dependent manner according to the number of miRNA target sites in each mRNA (p = 10-139). Conversely, we observed that in anx/anx cortex mRNAs predicted to be targeted by miRNAs were preferentially downregulated (p < 10-74), suggesting a de-regulation of genes targeted by miRNAs in two brain areas in anx/anx mice. A closer look to the mRNA transcriptome allowed us to identify upregulation of five miRISC genes, including Dgcr8 and Fmr1, and Ago2, which were later confirmed by Real Time PCR. The results suggest that miRNA machinery might be impaired in anx/anx mice and propose its involvement in inflammatory/cancer-associated anorexia-cachexia. The data also support the previously reported link between miRNA machinery and ataxia. Further functional studies and the cloning of the anx gene should be done in order to elucidate the causality of miRNA machinery and miRNA target de-regulation, its relation with the anx/anx phenotype and to propose this mouse as a model for miRNA research. Total RNA expression profile comparison between 3 pairs of anx/anx mice and wild type littermates in brain neocortex. MicroRNA expression profile comparison between 3 pairs of anx/anx mice and wild type littermates in brain neocortex.

ORGANISM(S): Mus musculus

SUBMITTER: Lauro Sumoy

PROVIDER: E-GEOD-26003 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

ACCESS DATA

Publications

Aberrant brain microRNA target and miRISC gene expression in the anx/anx anorexia mouse model.

Mercader Josep M JM González Juan R JR Lozano Juan José JJ Bak Mads M Kauppinen Sakari S Sumoy Lauro L Dierssen Mara M Fernández-Aranda Fernando F Visa Joana J Gratacòs Mònica M Estivill Xavier X

Gene 20120130 2

The anorexia mouse model, anx/anx, carries a spontaneous mutation not yet identified and homozygous mutants are characterized by anorexia-cachexia, hyperactivity, and ataxia. In order to test if the microRNA function was altered in these mice, hypothalamus and cortex transcriptomes were evaluated and the data was analyzed taking into account the presence of microRNA target sites. Subsequent validation of the expression of a subset of miRISC coding genes and microRNA targets was performed by TaqM ...[more]

PMID: 22310387

Similar Datasets

Project description:Epidermal growth factor (EGF) is a key regulatory growth factor activating a myriad of processes affecting cell proliferation and survival that are relevant to normal development and disease. Here we have used a combined approach to study the EGF dependent transcriptome of HeLa cells. We obtained mRNA expression profiles using multiple long oligonucleotide based microarray platforms (from Agilent, Operon, Febit, and Illumina) in combination with digital gene expression profiling (DGE) with the Illumina Genome Analyzer I (GA-I). By applying a procedure for cross-platform data meta-analysis based on rank product and global ancova tests, we establish a well validated gene set with transcript levels altered after EGF treatment. We used this robust gene list to build higher order networks of gene interaction by interconnecting associated networks, supporting and extending the important role of the EGF signaling pathway in cancer. In addition, we found a whole new set of genes previously unrelated to the currently accepted EGF associated cellular functions, among which are metallothionein genes. We propose the use of global genomic cross-validation to generate more reliable datasets derived from high content technologies (microarrays or deep sequencing). This approach should help to improve the confidence of downstream in silico functional inference analyses based on high content data. Keywords: treated vs. untreated comparison, time course Time course experiment comparing HeLa gene expression in response to EGF analyzed on different microarray platforms (Agilent, IMPPC, Illumina, and Operon) and by digital gene expression using short read high throughput tag sequencing. Three independent experiments were performed where HeLa cells were serum deprived for 24 hours and were either left untreated or treated with EGF for 6, and 24 h and harvested for RNA extraction. Technical dye swap duplicates were performed for each of the three biological replicates in both time points. Comparative genomic hybridization of HeLa cell genomic DNA versus poooled genomic DNA from blood obtained from human females conducted on commercial oligonucleotide microarrays (Human Genome CGH Microarray Kit 244A, Agilent Technologies) in order to assess DNA dosage dependence of gene expression levels and response to EGF. Digital gene expression using short read high throughput tag sequencing data submitted to NCBI's SRA

Dataset Information

Aberrant brain miRNA target and miRISC gene expression in the anx/anx anorexia mouse model

Publications

Aberrant brain microRNA target and miRISC gene expression in the anx/anx anorexia mouse model.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets