The construction of a panel of uniquely useful mouse strains means that geneticists who want to dissect complex traits now have a full deck of cards to play with.

Chromosome-substitution strains (CSSs), in which a single chromosome comes from one inbred strain (the donor; A) and the rest come from another (the host; B), are not a new idea. However, Jonathan Singer and colleagues are the first to construct a complete panel of strains for a vertebrate species — one for each autosome, sex chromosome and for the mitochondria.

The principle behind the use of CSSs to dissect complex traits is elegantly simple: if a CSS differs from the host strain in any given phenotype, then at least one quantitative trait locus (QTL) that influences that phenotype is present on the substituted chromosome. So, with a full panel, QTLs for the trait of interest can be quickly localized to chromosomes.

Creating the panel in the first place was not quite so easy. Singer et al. needed more than 17,000 mice and 7 years of work to create their mouse-CSS panel from inbred donor (A/J) and host (C57B/6J) strains that differ in many complex traits. Although it is time-consuming and requires a complete genetic map, the construction strategy is conceptually straightforward: progeny with non-recombinant copies of the desired chromosome are successively backcrossed to the host strain, to produce progeny that are heterosomic for that chromosome (A/B); these are subsequently intercrossed to obtain homosomic progeny (A/A).

However, the end result is worth the effort: the authors chromosomally localized 150 QTLs — one or more for nearly all the 53 complex traits that are related to sterol levels, diet-induced obesity, anxiety and amino-acid levels that they attempted to dissect with the complete panel. They also showed that traits can be mapped to specific locations on the chromosomes through follow-up crosses to the host strain.

The mouse-CSS panel is now available to all through the Jackson Laboratory. However, the lessons that have been learned during the construction process might be more important than this specific panel: in a matter of years, equivalent panels could be derived for any given host and donor strains — for example, from mouse or rat strains that vary in different traits.