Age-dependent amelioration of hypoplastic anemia in Ws/Ws rats with a small deletion at the kinase domain of c-kit.
The white-spotting (Ws) locus of rats represents a 12-base deletion of the c-kit receptor tyrosine kinase. Homozygous Ws/Ws rats are deficient in melanocytes, mast cells, and erythrocytes. Although mice possessing two mutant alleles at the c-kit (W) locus, such as mice of W/Wv genotype, show severe anemia even in adult age, the anemia of Ws/Ws rats remarkably ameliorated with age. We investigated the mechanism of the age-dependent amelioration. Bone marrow cells of Ws/Ws rats did not form macroscopic colonies in the spleen of irradiated rats, and the concentration of burst-forming unit-erythroid in the marrow of Ws/Ws rats was comparable with that of +/+ rats. Therefore, the increase in morphologically identifiable erythroid precursors in the marrow of Ws/Ws rats was attributed to the increased concentration of colony-forming unit-erythroid (CFU-E). Furthermore, the increase in CFU-E appeared to result from the increased concentration of erythropoietin (EPO). Because injections of relatively low doses of EPO cured the slight anemia that remained in adult Ws/Ws rats, CFU-E and/or its immediate precursors of Ws/Ws rats appeared to be more sensitive to EPO than those of W/Wv mice, in which a huge dose of EPO was necessary to cure the anemia.
Morimoto
M
M
Department of Pathology, Osaka University Medical School, Japan.
Kasugai
T
T
Tei
H
H
Jippo-Kanemoto
T
T
Kanakura
Y
Y
Kitamura
Y
Y
D000367:Age Factors; D000741:Anemia, Aplastic / Q000235:genetics / Q000517:prevention & control* / Q000628:therapy; D000818:Animals; D004921:Erythropoietin / Q000097:blood / Q000627:therapeutic use; D017353:Gene Deletion; D005838:Genotype; D006400:Hematocrit; D051379:Mice; D008810:Mice, Inbred C57BL; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D019009:Proto-Oncogene Proteins c-kit; D051381:Rats; D011922:Rats, Mutant Strains; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*; D016184:Receptors, Colony-Stimulating Factor / Q000235:genetics*; D011994:Recombinant Proteins / Q000627:therapeutic use
D011518:Proto-Oncogene Proteins; D016184:Receptors, Colony-Stimulating Factor; D011994:Recombinant Proteins; D004921:Erythropoietin; D019009:Proto-Oncogene Proteins c-kit; D020794:Receptor Protein-Tyrosine Kinases