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Cell Rep. 2017 Nov 21;21(8):2313-2325. doi: 10.1016/j.celrep.2017.10.093.

Extensive Homeostatic T Cell Phenotypic Variation within the Collaborative Cross.

Author information

1
Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
2
Division of Bioinformatics and Computational Biology, Department of Medical Informatics and Clinical Epidemiology, Oregon Health and Science University, Portland, OR 97239, USA; OHSU Knight Cancer Center Institute, Oregon Health and Science University, Portland, OR 97239, USA.
3
Oregon Clinical and Translational Research Institute, Oregon Health and Science University, Portland, OR 97239, USA.
4
Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
5
Division of Bioinformatics and Computational Biology, Department of Medical Informatics and Clinical Epidemiology, Oregon Health and Science University, Portland, OR 97239, USA; OHSU Knight Cancer Center Institute, Oregon Health and Science University, Portland, OR 97239, USA; Oregon Clinical and Translational Research Institute, Oregon Health and Science University, Portland, OR 97239, USA.
6
Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA; Department of Global Health, University of Washington, Seattle, WA 98195, USA. Electronic address: jlund@fredhutch.org.

Abstract

The Collaborative Cross (CC) is a panel of reproducible recombinant inbred mouse strains with high levels of standing genetic variation, affording an unprecedented opportunity to perform experiments in a small animal model containing controlled genetic diversity while allowing for genetic replicates. Here, we advance the utility of this unique mouse resource for immunology research because it allows for both examination and genetic dissection of mechanisms behind adaptive immune states in mice with distinct and defined genetic makeups. This approach is based on quantitative trait locus mapping: identifying genetically variant genome regions associated with phenotypic variance in traits of interest. Furthermore, the CC can be utilized for mouse model development; distinct strains have unique immunophenotypes and immune properties, making them suitable for research on particular diseases and infections. Here, we describe variations in cellular immune phenotypes across F1 crosses of CC strains and reveal quantitative trait loci responsible for several immune phenotypes.

KEYWORDS:

Collaborative Cross; QTL mapping; adaptive immunity; immunogenetics; mouse models; regulatory T cells

PMID:
29166619
PMCID:
PMC5728448
DOI:
10.1016/j.celrep.2017.10.093
[Indexed for MEDLINE]
Free PMC Article

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