Hematologic abnormalities of the immunodeficient mouse mutant, viable motheaten (mev).
Animal, Colony-Forming-Units-Assay, Colony-Stimulating-Factors, Erythroblasts: pa, Erythropoietin: bl, Female, Granulocytes: pa, Hematopoietic-Stem-Cells: pa, Immunologic-Deficiency-Syndromes: bl, pp, pa, Lymphokines: bi, Macrophages: pa, Male, Mice, Mice-Inbred-CBA, Mice-Inbred-C57BL, Mice-Inbred-DBA, Mice-Mutant-Strains, SUPPORT-U-S-GOVT-P-H-S
Exp Hematol 1989 Feb; 17(2):81-7.
CA40575, CA39266, CA20408
We have studied the hematopoietic system of the immunodeficient mouse mutant, viable motheaten (mev/mev). These mice usually die by 9 weeks of age from severe pneumonitis. The lungs at that time are infiltrated with granulocytes, macrophages, and lymphocytes. Granulocyte and macrophage precursor cells (CFU-GM) are dramatically increased in the spleens of mev/mev mice, whereas the bone marrow population of these precursors is decreased when compared with littermate control animals. The CFU-GM population retained its normal dependence on granulocyte-macrophage colony-stimulating factor (GM-CSF) for proliferation and differentiation. In contrast, the frequency of an erythroid precursor (CFU-E) was dramatically increased in spleen and showed increased sensitivity to erythropoietin (Epo). Moreover, a splenic CFU-E subpopulation formed normally appearing erythroid colonies in the absence of exogenous Epo. The bone marrow CFU-E population was significantly diminished in size when compared with either wildtype C57BL/6J mice or mice heterozygous for the mev allele. Unlike the CFU-E population, erythroid burst-forming unit (BFU-E) frequency in mev/mev mice was diminished both in bone marrow and in spleen, although the total number of splenic BFU-E was increased because of splenomegaly in these animals. BFU-E retained their dependence on the presence of both Epo and a source of interleukin 3 (IL-3) for proliferation and differentiation into erythroid bursts. Spleen cells from mev/mev mice, when stimulated in vitro with pokeweed mitogen, failed to produce significant quantities of IL-3. Comparison with medium or +/mev heterozygotes revealed that mev/mev spleen cell-conditioned medium showed a 40-fold reduction in burst-promoting activity. Thus, in viable motheaten mice, there is a major shift in hematopoiesis from bone marrow to spleen, which is accompanied by a diminished capacity of spleen cells to produce burst-promoting activity. These data and those from other studies suggest that the hematopoietic microenvironment of marrow may be impaired in this mutant.
Hematologic abnormalities of the immunodeficient mouse mutant, viable motheaten (mev). Exp Hematol 1989 Feb; 17(2):81-7.