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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.

Original publication




Journal article


Nat Genet

Publication Date





1197 - 1202


Animals, Animals, Outbred Strains, Anxiety, Base Sequence, Chromosome Mapping, Genetic Complementation Test, Mice, Mice, Inbred Strains, Mosaicism, Quantitative Trait, Heritable, RGS Proteins