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Genetic dissection of a behavioral quantitative trait locus shows that Rgs2 modulates anxiety in mice

Nature Genetics volume 36, pages 1197–1202 (2004)Cite this article

Abstract

Here we present a strategy to determine the genetic basis of variance in complex phenotypes that arise from natural, as opposed to induced, genetic variation in mice. We show that a commercially available strain of outbred mice, MF1, can be treated as an ultrafine mosaic of standard inbred strains and accordingly used to dissect a known quantitative trait locus influencing anxiety. We also show that this locus can be subdivided into three regions, one of which contains Rgs2, which encodes a regulator of G protein signaling. We then use quantitative complementation to show that Rgs2 is a quantitative trait gene. This combined genetic and functional approach should be applicable to the analysis of any quantitative trait.

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Figure 1: Single-marker and multipoint HAPPY QTL mapping in MF1 mice.
Figure 2: Reconstruction of MF1 haplotypes as inbred strain mosaics.

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Acknowledgements

We thank J. Penninger for providing the Rgs2-mutant mice and S. McCormick for comments on the manuscript. This work was funded by the Wellcome Trust.

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Author notes

  1. Binnaz Yalcin and Saffron A G Willis-Owen: These authors contributed equally to this work.

Authors and Affiliations

  1. Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford, OX3 7BN, UK

    Binnaz Yalcin, Saffron A G Willis-Owen, Jan Fullerton, Anjela Meesaq, Richard R Copley, Andrew P Morris, Jonathan Flint & Richard Mott

  2. Department of Experimental Psychology, University of Oxford, Oxford, UK

    Robert M Deacon & J Nicholas P Rawlins

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  1. Binnaz Yalcin
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  2. Saffron A G Willis-Owen
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Correspondence to Jonathan Flint or Richard Mott.

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Supplementary information

Supplementary Table 1

Comparison between C57BL6/J wild type (wt) and Rgs2 homozygous knockout (Mutant) mice. (PDF 5 kb)

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Yalcin, B., Willis-Owen, S., Fullerton, J. et al. Genetic dissection of a behavioral quantitative trait locus shows that Rgs2 modulates anxiety in mice. Nat Genet 36, 1197–1202 (2004). https://doi.org/10.1038/ng1450

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