title: Mechanisms of compensation of hemolytic anemia in a lactate dehydrogenase mouse mutant.
abstract: Hemopoiesis was studied in homozygous lactate dehydrogenase (LDH) mutant mice not showing noticeable impairment in viability and fertility but afflicted with a severe hemolytic anemia. In order to investigate the mechanisms of erythropoietic compensation, the numbers of multipotent hemopoietic stem cells (CFU-S), myeloid (GM-CFC), and early and late erythroid progenitors (BFU-E and CFU-E) in femur and spleen were determined, and the total body content of each cell type was computed. While the total CFU-S and GM-CFC numbers showed only slight deviations from normal, the total BFU-E pool was 1.4 and the CFU-E pool 18 times enlarged. No difference in cell cycle status could be detected in these compartments by means of tritiated thymidine (3H-TdR) suicide in vitro. However, splenic erythroblasts of homozygous LDH mutants had a shorter DNA synthesis time and a higher labeling index compared to the wild type mice. It is concluded that the hemolysis is compensated at a lower level of red blood cell count primarily by an increase in the total number of late erythroid progenitors resulting from roughly four extra divisions, and secondarily by an increase in the flux through the recognizable erythroblast compartments, predominantly a space-saving mechanism.
mesh_terms: D000743:Anemia, Hemolytic / Q000097:blood / Q000201:enzymology* / Q000235:genetics; D000818:Animals; D001854:Bone Marrow Cells; D002453:Cell Cycle; D003114:Colony-Forming Units Assay; D004900:Erythroblasts / Q000166:cytology; D004920:Erythropoiesis; D004921:Erythropoietin / Q000097:blood; D006098:Granulocytes / Q000166:cytology; D006412:Hematopoietic Stem Cells / Q000166:cytology; D006720:Homozygote; D007700:Kinetics; D007770:L-Lactate Dehydrogenase / Q000097:blood* / Q000235:genetics; D008264:Macrophages / Q000166:cytology; D051379:Mice; D008817:Mice, Mutant Strains / Q000235:genetics*; D013154:Spleen / Q000166:cytology
chemical_list: D004921:Erythropoietin; D007770:L-Lactate Dehydrogenase