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The mouse has been a powerful force in elucidating the genetic basis of human physiology and pathophysiology. From its beginnings as the model organism for cancer research and transplantation biology to the present, when dissection of the genetic basis of complex disease is at the forefront of genomics research, an enormous and remarkable mouse resource infrastructure has accumulated. This review summarizes those resources and provides practical guidelines for their use, particularly in the analysis of quantitative traits.

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Historically our ability to identify genetic variants underlying complex behavioral traits in mice has been limited by low mapping resolution of conventional mouse crosses. The newly developed Diversity Outbred (DO) population promises to deliver improved resolution that will circumvent costly fine mapping studies. The DO is derived from the same founder strains as the Collaborative Cross (CC), including three wild derived strains. Thus the DO provides more allelic diversity and greater potential for new discovery compared to crosses involving standard mouse strains. We have characterized 283 male and female DO mice using open-field, light-dark box, tail-suspension, and visual-cliff avoidance tests to generate 38 behavioral measures. We identified several quantitative trait loci (QTL) for these traits with support intervals ranging from 1 to 3 Mb in size. These intervals contain relatively few genes (ranging from 5 to 96). For a majority of QTL, using the founder allelic effects together with whole genome sequence data, we could further narrow the positional candidates. Several QTL replicate previously published loci. Novel loci were also identified for anxiety- and activity-related traits. Half of the QTLs are associated with wild-derived alleles, confirming the value to behavioral genetics of added genetic diversity in the DO. In the presence of wild-alleles we sometimes observe behaviors that are qualitatively different from the expected response. Our results demonstrate that high-precision mapping of behavioral traits can be achieved with moderate numbers of DO animals, representing a significant advance in our ability to leverage the mouse as a tool for behavioral genetics.

In the red blood cell (RBC), adducin is present primarily as tetramers of ␣-and ␤-subunits at spectrin-actin junctions, or junctional complexes. Mouse RBCs also contain small amounts of ␥-adducin. Platelets contain ␣-and ␥-adducin only. Adducin functions as a barbed-end actin capping protein to regulate actin filament length and recruits spectrin to the ends of actin filaments. To further define adducin's role in vivo, we generated ␣-adducin knockout mice. ␣-Adducin is absent in all tissues examined in homozygous null mice. In RBCs, ␤-and ␥-adducin are also absent, indicating that ␣-adducin is the limiting subunit in tetramer formation at the spectrin-actin junction. Similarly, ␥-adducin is absent in ␣-null platelets. ␣-