Genes for Difference in Eosinophilic Phenotype between MES and BN.MES-Cybames Rats Are on Chromosomes 9, 5, and 1

Abstract

Abstract:The Matsumoto Eosinophilia Shinshu (MES) rat strain develops hereditary blood eosinophilia due to the mutant Cyba mes gene. In contrast, BN.MES-Cyba mes congenic rats, in which the mutant Cyba mes gene introduced into the background of the BN strain, have a normal blood eosinophil level despite showing robust proliferation of eosinophils in the bone marrow. However, the congenic rats manifest focal necrosis with eosinophilic infiltration in the liver, a phenotype rarely observed in the original MES rat strain. To elucidate the genetic basis for the strain differences, (MES × BN.MES-Cyba mes )F 2 rats were bred, and genetic analyses of phenotypes for eosinophilia were performed. Blood and bone marrow eosinophil levels in the F 2 rats showed broad distributions, suggesting that the traits were under the influence of multiple genes. Genetic association studies revealed that BN-derived marker loci on chromosomes 9 and 5 were responsible for the increase in eosinophil level in the bone marrow, decrease in blood eosinophil level, and the induction of focal necrosis with eosinophilic infiltration in the liver. The BN-derived allele of the marker gene on chromosome 1 was responsible for the decrease of both bone marrow and blood eosinophil levels. These data suggest the existence of genes characterizing/distinguishing the eosinophilic phenotypes of MES and BN.MES-Cyba mes on these chromosomes, and form the basis for positional cloning studies of the genes. These studies will advance the understanding of the mechanisms involved in eosinophil mobilization from the bone marrow and recruitment to the organs.

<i>Cyba</i> and <i>Nox2</i> mutant rats show different incidences of eosinophilia in the genetic background- and sex-dependent manner

“…Previously, we established another congenic rat strain BN.MES- Cyba mes , and found that blood eosinophilia was completely suppressed in the congenic rats [ 11 ]. Subsequently, we proved by breeding (MES x BN.MES- Cyba mes )F 2 rat progenies, the presence of quantitative trait loci that differentiate the blood eosinophil level of the two rat strains [ 24 ]. It is likely that F344/N rats also possess gene(s) that suppresses the development of blood eosinophilia under loss of NOX2 NADPH oxidase or CYBA function.…”