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Mapping Infant Immunity with Minimal Input: Integrative Single-cell and Multiomic Profiling
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Using the emerging Collaborative Cross to probe the immune system.

J Phillippi1, Y Xie2, D R Miller3

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

Genes and Immunity
|November 8, 2013
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Summary
This summary is machine-generated.

The Collaborative Cross mouse model reveals significant genetic diversity in immune cell traits. This mouse panel is valuable for studying complex immune system variations and their genetic underpinnings.

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Area of Science:

  • Immunology
  • Genetics
  • Mouse Models

Background:

  • The Collaborative Cross (CC) is a panel of recombinant inbred mouse strains derived from eight founder strains.
  • Each CC strain is genetically distinct, offering a powerful resource for genetic studies.
  • Understanding immune cell variation is crucial for dissecting complex diseases.

Purpose of the Study:

  • To investigate the genetic basis of immunophenotypic variation within the Collaborative Cross mouse model.
  • To identify genetic loci controlling specific immune cell populations and expression levels.
  • To assess the utility of the pre-CC resource for immunophenotype research.

Main Methods:

  • Analysis of lymphocyte and antigen-presenting cell subsets in CC founder strains, pre-CC strains, and F1 offspring.
  • Genome-wide association studies (GWAS) using inferred haplotypes to detect quantitative trait loci (QTL).
  • Comparison of genetic architectures for traits like B-to-T cell ratio and CD23 expression.

Main Results:

  • Significant immunophenotypic variation was observed among CC founders and even greater diversity in pre-CC strains.
  • GWAS identified significant loci controlling B-to-T cell ratio, CD8 T-cell numbers, and CD11c/CD23 expression.
  • CD23 variation was largely explained by additive genetics at a single locus containing the Fcer2a gene, while B-to-T ratio showed complex genetic control.

Conclusions:

  • The pre-CC resource demonstrates high utility for studying immunophenotypes and integrating genetic data.
  • The CC mouse model is valuable for dissecting the genetic architecture of immune traits.
  • Observed extreme immunophenotypes may have pleiotropic effects in other CC-based experiments.