Study on pathogenesis of eosionophilia with MES congenic rat developing human eosinophilia

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The MES rat, Dr. Matsumoto the applicant of this grant found out, spontaneously develops eosinophilia and eosinophil-related inflammatory lesions in many organs. As part of investigation into the cause of eosinophilia in MES rats, genetic and hematological analyses were carried out with congenic rats (BN.MES-eos1). As a first step, peripheral blood hematology (OHM bone marrow eosinophil count and gross pathology were carried out on the F2 progeny obtained by mating congenic (BN.MES-eosl) and MES rats. Of the 134 F2 animals, 79 (59%) showed white spot in the liver, which was histopathologically diagnosed as focal necrosis with eosinophil infiltration. Remarkably, almost all rats with sever white spot lesions had eosinophilic hyperplasia (20%<) in the bone marrow. Of these 88 rats with marrow eosinophilic hyperplasia, 37 rats did not show eosinophilia (<500/u L) in the peripheral blood. These findings of marrow eosinophilic hyperplasia without peripheral eoisonophilia were clinically similar to those in BN.MES-eos1 rats. To elucidate the genetic roles of hematological pathology, gene mapping study are carried out. As a results, it was found that the major locus for eosinophilia was located on chromosome 19 (Eosl) and another quantitative trait locus showing suggestive linkage for eosinophilia on choromosome 1 (Eos-g). Additionally, the findings of a third locus for esinophilia also located on chromosome 2 (EosE.0, suggesting that eosinophilia in MES is a rather complex genetic trait.