AUTHOR=Krayem Imtissal , Sohrabi Yahya , Javorková Eliška , Volkova Valeriya , Strnad Hynek , Havelková Helena , Vojtíšková Jarmila , Aidarova Aigerim , Holáň Vladimír , Demant Peter , Lipoldová Marie 

TITLE=Genetic Influence on Frequencies of Myeloid-Derived Cell Subpopulations in Mouse

JOURNAL=Frontiers in Immunology

VOLUME=12

YEAR=2022

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2021.760881

DOI=10.3389/fimmu.2021.760881

ISSN=1664-3224

ABSTRACT=<p>Differences in frequencies of blood cell subpopulations were reported to influence the course of infections, atopic and autoimmune diseases, and cancer. We have discovered a unique mouse strain B10.O20 containing extremely high frequency of myeloid-derived cells (MDC) in spleen. B10.O20 carries 3.6% of genes of the strain O20 on the C57BL/10 genetic background. It contains much higher frequency of CD11b<sup>+</sup>Gr1<sup>+</sup> cells in spleen than both its parents. B10.O20 carries O20-derived segments on chromosomes 1, 15, 17, and 18. Their linkage with frequencies of blood cell subpopulations in spleen was tested in F<sub>2</sub> hybrids between B10.O20 and C57BL/10. We found 3 novel loci controlling MDC frequencies: <italic>Mydc1, 2</italic>, and <italic>3</italic> on chromosomes 1, 15, and 17, respectively, and a locus controlling relative spleen weight (<italic>Rsw1</italic>) that co-localizes with <italic>Mydc3</italic> and also influences proportion of white and red pulp in spleen. <italic>Mydc1</italic> controls numbers of CD11b<sup>+</sup>Gr1<sup>+</sup> cells. Interaction of <italic>Mydc2</italic> and <italic>Mydc3</italic> regulates frequency of CD11b<sup>+</sup>Gr1<sup>+</sup> cells and neutrophils (Gr1<sup>+</sup>Siglec-F<sup>-</sup> cells from CD11b<sup>+</sup> cells). Interestingly, <italic>Mydc3</italic>/<italic>Rsw1</italic> is orthologous with human segment 6q21 that was shown previously to determine counts of white blood cells. Bioinformatics analysis of genomic sequence of the chromosomal segments bearing these loci revealed polymorphisms between O20 and C57BL/10 that change RNA stability and genes’ functions, and we examined expression of relevant genes. This identified potential candidate genes <italic>Smap1, Vps52, Tnxb</italic>, and <italic>Rab44.</italic> Definition of genetic control of MDC can help to personalize therapy of diseases influenced by these cells.</p>