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High-resolution genetic mapping of mammalian motor activity levels in mice.
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- Author(s): Kas, M. J. H.; de Mooij-van Malsen, J. G.; de Krom, M.; van Gassen, K. L. I.; van Lith, H. A.; Olivier, B.; Oppelaar, H.; Hendriks, J.; de Wit, M.; Groot Koerkamp, M. J. A.; Holstege, F. C. P.; van Oost, B. A.; de Graan, P. N. E.
- Source:
Genes, Brain & Behavior; Feb2009, Vol. 8 Issue 1, p13-22, 10p, 2 Charts, 4 Graphs- Subject Terms:
- Source:
- Additional Information
- Abstract: The generation of motor activity levels is under tight neural control to execute essential behaviors, such as movement toward food or for social interaction. To identify novel neurobiological mechanisms underlying motor activity levels, we studied a panel of chromosome substitution (CS) strains derived from mice with high (C57BL/6J strain) or low motor activity levels (A/J strain) using automated home cage behavioral registration. In this study, we genetically mapped the expression of baseline motor activity levels (horizontal distance moved) to mouse chromosome 1. Further genetic mapping of this trait revealed an 8.3-Mb quantitative trait locus (QTL) interval. This locus is distinct from the QTL interval for open-field anxiety-related motor behavior on this chromosome. By data mining, an existing phenotypic and genotypic data set of 2445 genetically heterogeneous mice ( ), we confirmed linkage to the peak marker at 79 970 253 bp and refined the QTL to a 312-kb interval containing a single gene ( A830043J08Rik). Sequence analysis showed a nucleotide deletion in the 3′ untranslated region of the Riken gene. Genome-wide microarray gene expression profiling in brains of discordant F
2 individuals from CS strain 1 showed a significant upregulation of Epha4 in low-active F2 individuals. Inclusion of a genetic marker for Epha4 confirmed that this gene is located outside of the QTL interval. Both Epha4 and A830043J08Rik are expressed in brain motor circuits, and similar to Epha4 mutants, we found linkage between reduced motor neurons number and A/J chromosome 1. Our findings provide a novel QTL and a potential downstream target underlying motor circuitry development and the expression of physical activity levels. [ABSTRACT FROM AUTHOR] - Abstract: Copyright of Genes, Brain & Behavior is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
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