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...

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Bibliographic Details
Published in:Blood 1993-12, Vol.82 (11), p.3315-3320
Main Authors: Morimoto, Masahiro, Kasugai, Tsutomu, Tei, Hideki, Jippo-Kanemoto, Tomoko, Kanakura, Yuzuru, Kitamura, Yukihiko
Format: Article
Language:English
Subjects:
Age Factors
Anemia, Aplastic - genetics
Anemia, Aplastic - prevention & control
Anemia, Aplastic - therapy
Anemias. Hemoglobinopathies
Animals
Biological and medical sciences
Diseases of red blood cells
Erythropoietin - blood
Erythropoietin - therapeutic use
Gene Deletion
Genotype
Hematocrit
Hematologic and hematopoietic diseases
Medical sciences
Mice
Mice, Inbred C57BL
Proto-Oncogene Proteins - genetics
Proto-Oncogene Proteins c-kit
Rats
Rats, Mutant Strains
Receptor Protein-Tyrosine Kinases - genetics
Receptors, Colony-Stimulating Factor - genetics
Recombinant Proteins - therapeutic use
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Summary: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.
ISSN:0006-4971
1528-0020
DOI:10.1182/blood.V82.11.3315.3315