5.c-kitミュータントラット : ―好塩基球とマスト細胞の分化―

概要

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Production of mast cells is regulated by fibroblast-dependent and T-cell-dependent mechanisms. The fibroblast-dependent mechanism is mediated by the c-kit receptor tyrosine kinase encoded by the mouse W locus and its ligand encoded by the mouse Sl locus. Mice possessing a double gene dose of mutant alleles at either W (c-kit) or Sl locus are deficient in mast cells. We recently found that homozygous mutant rats at the Ws locus are also deficient in mast cells. Because the phenotype of Ws/Ws rats resembled the phenotype of the W (c-kit) mutant mice, we characterized the c-kit gene of Ws/Ws rats. When compared with the c-kit cDNA of control +/+ rats, a deletion of 12 bases was found in the c-kit cDNA of Ws/Ws rats. Control +/+ and Ws/Ws rats were infected with Nippostrongylus brasil iensis (NB) . A 60-fold increase of basophils and a 10-fold increase of mucosal-type mast cells (MMC) occurred in the +/+ rats. A 60-fold increase of basophils was observed in the Ws/Ws rats as well. Although no MMC were detectable in the small intestine of non-infected Ws/Ws rats, MMC did develop after the infection of NB. However, the peak value of MMC in the small intestine of infected Ws/ Ws rats was about 10 % that of the infected +/+ rats. This suggests that only T cell-dependent mechanism is enough for production of basophils and that T cell-dependent and fibroblast-dependent mechanisms are necessary for production of MMC. In contrast with the marked increase of basophils and MMC, connective tissue-type mast cells (CTMC) in the skin and bone marrow did not increase in the + / + rats and did not develop in the Ws/ Ws rats. This suggests that fibroblast-dependent mechanism is indispensable for development of CTMC. Taken together, the Ws/Ws rats are useful model for discrimination of differentiation mechanisms between basophils, MMC, and CTMC.

5.c-<I>kit</I>ミュータントラット : ―好塩基球とマスト細胞の分化―

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