Age-dependent amelioration of hypoplastic anemia in Ws/Ws rats with a small deletion at the kinase domain of c-kit.

Abstract:

: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.

journal_name

Blood

journal_title

Blood

authors

Morimoto M,Kasugai T,Tei H,Jippo-Kanemoto T,Kanakura Y,Kitamura Y

subject

Has Abstract

pub_date

1993-12-01 00:00:00

pages

3315-20

issue

11

eissn

0006-4971

issn

1528-0020

journal_volume

82

pub_type

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