Faculty Research 1980 - 1989

Title

Hematologic abnormalities of the immunodeficient mouse mutant, viable motheaten (mev).

Document Type

Article

Publication Date

1989

Keywords

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

JAX Location

1741

JAX Source

Exp Hematol 1989 Feb; 17(2):81-7.

Grant

CA40575, CA39266, CA20408

Abstract

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.

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