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Using the emerging Collaborative Cross to probe the immune system

Genes & Immunity volume 15, pages 38–46 (2014)Cite this article

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Abstract

The Collaborative Cross (CC) is an emerging panel of recombinant inbred (RI) mouse strains. Each strain is genetically distinct but all descended from the same eight inbred founders. In 66 strains from incipient lines of the CC (pre-CC), as well as the 8 CC founders and some of their F1 offspring, we examined subsets of lymphocytes and antigen-presenting cells. We found significant variation among the founders, with even greater diversity in the pre-CC. Genome-wide association using inferred haplotypes detected highly significant loci controlling B-to-T cell ratio, CD8 T-cell numbers, CD11c and CD23 expression. Comparison of overall strain effects in the CC founders with strain effects at QTL in the pre-CC revealed sharp contrasts in the genetic architecture of two traits with significant loci: variation in CD23 can be explained largely by additive genetics at one locus, whereas variation in B-to-T ratio has a more complex etiology. For CD23, we found a strong QTL whose confidence interval contained the CD23 structural gene Fcer2a. Our data on the pre-CC demonstrate the utility of the CC for studying immunophenotypes and the value of integrating founder, CC and F1 data. The extreme immunophenotypes observed could have pleiotropic effects in other CC experiments.

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Acknowledgements

The authors thank Dr Ellen Young, Cindy Hensley and Shaun Steele for their substantial assistance in data collection. The authors acknowledge NIH grants GM070683 (genotyping), P50 MH0903380/HG006582 (partial support for AB, FPMV, WV), GM104125 (partial support for AB, WV), F32 GM090667 (DLA), CA105417 (DWT, FVPM), and the Lineberger Comprehensive Cancer Center (JAF).

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Author notes

  1. J Phillippi, Y Xie, W Valdar and J A Frelinger: These authors have contributed equally to this work.

Authors and Affiliations

  1. Department of Immunobiology, University of Arizona, Tucson, AZ, USA

    J Phillippi, S H Krovi & J A Frelinger

  2. Department of Genetics, University of North Carolina, Chapel Hill, NC, USA

    Y Xie, D R Miller, T A Bell, A B Lenarcic, D L Aylor, F Pardo-Manuel de Villena & W Valdar

  3. Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, USA

    D R Miller, T A Bell, D L Aylor, F Pardo-Manuel de Villena & W Valdar

  4. Department of Computer Science, University of North Carolina, Chapel Hill, NC, USA

    Z Zhang

  5. Department of Genetics, North Carolina State University, Raleigh, NC, USA

    D W Threadgill

  6. Department of Computer Science, and the Jonsson Comprehensive Cancer Center, University of California, Los Angeles, CA, USA

    W Wang

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  1. J Phillippi
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Correspondence to W Valdar or J A Frelinger.

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Phillippi, J., Xie, Y., Miller, D. et al. Using the emerging Collaborative Cross to probe the immune system. Genes Immun 15, 38–46 (2014). https://doi.org/10.1038/gene.2013.59

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