Genes for Difference in Eosinophilic Phenotype between MES and BN.MES-Cybames Rats Are on Chromosomes 9, 5, and 1
Genes for Difference in Eosinophilic Phenotype between MES and BN.MES-Cybames Rats Are on Chromosomes 9, 5, and 1
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DOI：
10.1538/expanim.60.151
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发表时间：
2011-04-01
影响因子：
2.4
通讯作者：
Mori, Masayuki
中科院分区：
文献类型：
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作者：
Tomozawa, Hiroshi;Nishio, Ayako;Mori, Masayuki
松本嗜酸性粒细胞增多Shinshu（MES）大鼠品系由于突变Cyba（mes）基因而发生遗传性血液嗜酸性粒细胞增多。相比之下，BN.MES-Cyba（mes）同源大鼠（其中突变Cyba（mes）基因被引入BN品系的背景中）具有正常的血液嗜酸性粒细胞水平，尽管在骨髓中显示出嗜酸性粒细胞的稳健增殖。然而，同类大鼠表现出局灶性坏死伴肝脏嗜酸性粒细胞浸润，这是在原始MES大鼠品系中很少观察到的表型。为了阐明品系差异的遗传基础，饲养（MES x BN.MES-Cyba（mes））F-2大鼠，并进行嗜酸性粒细胞增多症表型的遗传分析。F-2代大鼠的血液和骨髓嗜酸性粒细胞水平呈广泛分布，表明这些性状受多个基因的影响。遗传关联研究表明，BN衍生的标记基因座的9号和5号染色体上负责骨髓嗜酸性粒细胞水平的增加，血液嗜酸性粒细胞水平的降低，并诱导局灶性坏死与嗜酸性粒细胞浸润的肝脏。1号染色体上标记基因的BN衍生等位基因负责骨髓和血液嗜酸性粒细胞水平的降低。这些数据表明存在表征/区分MES和BN的嗜酸性表型的基因。MES-Cyba（mes）在这些染色体上，并形成基因的定位克隆研究的基础。这些研究将促进对嗜酸性粒细胞从骨髓动员和向器官募集的机制的理解。
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 x 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.