Mapping Data

Experiment

• Experiment
  TEXT-QTL
• Chromosome
  7
• Reference
  J:304799 Dupont MSJ, et al., Host genetic control of natural killer cell diversity revealed in the Collaborative Cross. Proc Natl Acad Sci U S A. 2021 Mar 9;118(10):e2018834118
• ID
  MGI:6704966

Genes

Gene	Assay Type
Nkh1	visible phenotype
Fsnk2	visible phenotype

Notes

• Reference
  The Collaborative Cross (CC) is a large (~1,000 line) panel of recombinant inbred (RI) mouse strains being developed through a community effort (Churchill et al. 2004). The CC combines the genomes of eight genetically diverse founder strains - A/J, C57BL/6J, 129S1/SvImJ, NOD/ShiLtJ, NZO/HlLtJ, CAST/EiJ, PWK/PhJ, and WSB/EiJ - to capture nearly 90% of the known variation present in laboratory mice. CC strains are derived using a unique funnel breeding scheme. Once inbred, the RI CC lines can be used to generate thousands of potential 'outbred' but completely reproducible genomes through the generation of recombinant inbred crosses (RIX). The designation 'PreCC' is used to describe a mapping population of CC mice that is still at incipient stages of inbreeding.
  
  CTC (2004), Churchill, G. A., et al.. The Collaborative Cross, a community resource for the genetic analysis of complex traits. Nat Genet. 36, 1133-7.
• Experiment
  Natural killer (NK) cells are innate effectors armed with cytotoxic and cytokine-secreting capacities whose spontaneous antitumor activity is key to numerous immunotherapeutic strategies. The authors performed a comprehensive profiling of NK cells in the Collaborative Cross (CC), a collection of novel recombinant inbred mouse strains whose genetic diversity matches that of humans, thereby providing a unique and highly diverse small animal model for the study of immune variation. The authors demonstrate that NK cells from CC strains displayed a breadth of phenotypic and functional variation reminiscent of that reported for humans with regards to cell numbers, key marker expression, and functional capacities.
  
  CC recombinant inbred mice were purchased at the Systems Genetics Core Facility at the University of North Carolina at Chapel Hill or from the Jackson Laboratory and bred in the animal facility of the Institut Pasteur under Specific Pathogen Free (SPF) conditions.
  
  The authors included in each experiment at least one C57BL/6J mouse serving both as experimental control and reference for antibody staining. For the phenotyping experiments, they analyzed six mice for three strains (CC006, CC037, and CC059), four mice for two strains (CC013 and CC060), two mice for one line (CC039), and five mice for the remaining 26 strains.
  
  The authors assessed the phenotypic diversity of NK cells at homeostasis in adult mice in four different organs from 32 CC strains compared to control B6 mice. More specifically, they focused on the variation of NK cell numbers, differentiation stages as defined by CD27, CD11b, and KLRG1 expression patterns, and expression of other NK cell surface and intracellular markers, including CD94, DNAM-1, NKp46, and the transcriptions factors (TF) Eomesodermin (Eomes) and T-bet. The authors further assessed phenotypic NK cell variation through analysis of key surface and intracellular marker expression.
  
  The authors performed QTL mapping using R/QTL2 to reveal genetic loci associated to the variations in the traits they measured.
  
  Three significant QTL were identified (genome coordinates relative to GRCm38/mm10):
  
  Nkl1 (NK cell number in lung 1) maps to Chr 13: 85.8 - 93.93 Mb with a peak p-value of 0.0077. NZO/HlLtJ contributes the high allele at Nkl1.
  
  Nkh1 (NKp46 expression in hepatic NK cells 1) maps to Chr 7: 3.06 - 6.75 Mb with a peak p-value of 0.0018. C57BL/6J and WSB/EiJ contribute the low alleles at Nkh1.
  
  Fsnk1 (frequency of CD94+ splenic NK cells 1) maps to Chr 6: 128.22 - 137 Mb with a peak p-value of 0.008. CAST/EiJ and WSB/EiJ contribute the low alleles at Fcd94nk1.
  
  Six suggestive QTL were also identified:
  
  Nkcnm1 (NK cell number in the mLN 1) maps to Chr 4: 102.89 - 142.91 Mb.
  
  Flsnk1 (frequency of KLRG1+ NK cells in the liver and spleen 1) maps to Chr 19: 3.17 - 31.23 Mb.
  
  Fsnk2 (frequency of CD11b+ splenic NK cells 2) maps to Chr 7: 36.03 - 134.99 Mb.
  
  Fsnk3 (frequency of CD27/CD11b DP splenic NK cells 3) maps to Chr 10: 88.23 - 94.47 Mb.
  
  Fsnk4 (frequency of CD27/CD11b DP splenic NK cells 4) maps to Chr 13: 48.18 - 52.75 Mb.
  
  Fnkm1 (frequency of DNAM-1+ NK cells in the mLN 1) maps to Chr 2: 53.05 - 76.25 Mb.