Document Type
Article
Publication Date
6-25-2024
Original Citation
Oliveira T,
Merkenschlager J,
Eisenreich T,
Bortolatto J,
Yao K,
Gatti D,
Churchill G,
Nussenzweig M,
Breton G.
Quantitative trait loci mapping provides insights into the genetic regulation of dendritic cell numbers in mouse tissues. Cell Rep. 2024;43(6):114296.
Keywords
JMG, Animals, Dendritic Cells, Mice, Quantitative Trait Loci, Polymorphism, Single Nucleotide, Mice, Inbred C57BL, Cell Count, Chromosome Mapping, Homeostasis
JAX Source
Cell Rep. 2024;43(6):114296.
ISSN
2211-1247
PMID
38823019
DOI
https://doi.org/10.1016/j.celrep.2024.114296
Abstract
To explore the influence of genetics on homeostatic regulation of dendritic cell (DC) numbers, we present a screen of DCs and their progenitors in lymphoid and non-lymphoid tissues in Collaborative Cross (CC) and Diversity Outbred (DO) mice. We report 30 and 71 loci with logarithm of the odds (LOD) scores >8.18 and ranging from 6.67 to 8.19, respectively. The analysis reveals the highly polygenic and pleiotropic architecture of this complex trait, including many of the previously identified genetic regulators of DC development and maturation. Two SNPs in genes potentially underlying variation in DC homeostasis, a splice variant in Gramd4 (rs235532740) and a missense variant in Orai3 (rs216659754), are confirmed by gene editing using CRISPR-Cas9. Gramd4 is a central regulator of DC homeostasis that impacts the entire DC lineage, and Orai3 regulates cDC2 numbers in tissues. Overall, the data reveal a large number of candidate genes regulating DC homeostasis in vivo.
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