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  Genetic variation in hippocampal microRNA expression differences in C57BL/6 J X DBA/2 J (BXD) recombinant inbred mouse strains

Parsons, M. J., Grimm, C., Paya-Cano, J. L., Fernandes, C., Liu, L., Philip, V. M., et al. (2012). Genetic variation in hippocampal microRNA expression differences in C57BL/6 J X DBA/2 J (BXD) recombinant inbred mouse strains. BMC Genomics, 13, 476. doi:10.1186/1471-2164-13-476.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-000E-F07A-A Version Permalink: http://hdl.handle.net/11858/00-001M-0000-000E-F07B-8
Genre: Journal Article

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2012
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2012 Parsons et al.; licensee BioMed Central Ltd.

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 Creators:
Parsons, MMichael J.1, Author
Grimm, Christina2, Author              
Paya-Cano, Jose L.3, Author
Fernandes, Cathy3, Author
Liu, Lin3, Author
Philip, Vivek. M.4, Author
Chesler, Elissa J.5, Author
Nietfeld, W., Author
Lehrach, H., Author
Schalkwyk, L. C., Author
Affiliations:
1Mammalian Genetics Unit, Medical Research Council – Harwell, Oxfordshire, United Kingdom , ou_persistent22              
2In vitro Ligand Screening (Zoltán Konthur), Dept. of Vertebrate Genomics (Head: Hans Lehrach), Max Planck Institute for Molecular Genetics, Max Planck Society, Ihnestr. 63-74, Berlin, Germany, ou_1479653              
3Social, Genetic, and Developmental Psychiatry Centre, Institute of Psychiatry, London, King's College, London, UK , ou_persistent22              
4Graduate School of Genome Science and Technology, University of Tennessee, Knoxville, TN, USA , ou_persistent22              
5The Jackson Laboratory, Bar Harbor, Maine, USA , ou_persistent22              

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 Abstract: BACKGROUND: miRNAs are short single-stranded non-coding RNAs involved in post-transcriptional gene regulation that play a major role in normal biological functions and diseases. Little is currently known about how expression of miRNAs is regulated. We surveyed variation in miRNA abundance in the hippocampus of mouse inbred strains, allowing us to take a genetic approach to the study of miRNA regulation, which is novel for miRNAs. The BXD recombinant inbred panel is a very well characterized genetic reference panel which allows quantitative trait locus (QTL) analysis of miRNA abundance and detection of correlates in a large store of brain and behavioural phenotypes. RESULTS: We found five suggestive trans QTLs for the regulation of miRNAs investigated. Further analysis of these QTLs revealed two genes, Tnik and Phf17, under the miR-212 regulatory QTLs, whose expression levels were significantly correlated with miR-212 expression. We found that miR-212 expression is correlated with cocaine-related behaviour, consistent with a reported role for this miRNA in the control of cocaine consumption. miR-31 is correlated with anxiety and alcohol related behaviours. KEGG pathway analysis of each miRNA's expression correlates revealed enrichment of pathways including MAP kinase, cancer, long-term potentiation, axonal guidance and WNT signalling. CONCLUSIONS: The BXD reference panel allowed us to establish genetic regulation and characterize biological function of specific miRNAs. QTL analysis enabled detection of genetic loci that regulate the expression of these miRNAs. eQTLs that regulate miRNA abundance are a new mechanism by which genetic variation influences brain and behaviour. Analysis of one of these QTLs revealed a gene, Tnik, which may regulate the expression of a miRNA, a molecular pathway and a behavioural phenotype. Evidence of genetic covariation of miR-212 abundance and cocaine related behaviours is strongly supported by previous functional studies, demonstrating the value of this approach for discovery of new functional roles and downstream processes regulated by miRNA.

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Language(s): eng - English
 Dates: 2011-12-112012-09-052012-09-13
 Publication Status: Published online
 Pages: -
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 Rev. Method: -
 Identifiers: DOI: 10.1186/1471-2164-13-476
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Title: BMC Genomics
Source Genre: Journal
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Publ. Info: BioMed Central
Pages: - Volume / Issue: 13 Sequence Number: - Start / End Page: 476 Identifier: ISSN: 1471-2164
CoNE: https://pure.mpg.de/cone/journals/resource/111000136905010