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Publication : Hippocampal gene expression analysis highlights Ly6a/Sca-1 as candidate gene for previously mapped novelty induced behaviors in mice.

First Author  de Jong S Year  2011
Journal  PLoS One Volume  6
Issue  6 Pages  e20716
PubMed ID  21673958 Mgi Jnum  J:174141
Mgi Id  MGI:5051989 Doi  10.1371/journal.pone.0020716
Citation  de Jong S, et al. (2011) Hippocampal gene expression analysis highlights ly6a/sca-1 as candidate gene for previously mapped novelty induced behaviors in mice. PLoS One 6(6):e20716
abstractText  In this study, we show that the covariance between behavior and gene expression in the brain can help further unravel the determinants of neurobehavioral traits. Previously, a QTL for novelty induced motor activity levels was identified on murine chromosome 15 using consomic strains. With the goal of narrowing down the linked region and possibly identifying the gene underlying the quantitative trait, gene expression data from this F(2)-population was collected and used for expression QTL analysis. While genetic variation in these mice was limited to chromosome 15, eQTL analysis of gene expression showed strong cis-effects as well as trans-effects elsewhere in the genome. Using weighted gene co-expression network analysis, we were able to identify modules of co-expressed genes related to novelty induced motor activity levels. In eQTL analyses, the expression of Ly6a (a.k.a. Sca-1) was found to be cis-regulated by chromosome 15. Ly6a also surfaced in a group of genes resulting from the network analysis that was correlated with behavior. Behavioral analysis of Ly6a knock-out mice revealed reduced novelty induced motor activity levels when compared to wild type controls, confirming functional importance of Ly6a in this behavior, possibly through regulating other genes in a pathway. This study shows that gene expression profiling can be used to narrow down a previously identified behavioral QTL in mice, providing support for Ly6a as a candidate gene for functional involvement in novelty responsiveness.
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