Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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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

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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]

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