Reconstitution of the W/W(v) stem cell differentiation defect by infection with Rauscher leukemia virus
article
Hematopoietic stem cells of W/W(v) mice failed to produce macroscopically visible hematopoietic spleen colonies in irradiated recipient mice. Infection of W/W(v) mice of the spleen focus-forming virus-susceptible genotype Fv-2(ss) (DBA/2) or Fv-2(rs) (BD2F1) with Rauscher leukemia virus (RLV) restored the spleen colony-forming capacity of the stem cells. The resulting spleen colonies had normal size and cellularity; the frequency of and ratio between granulocyte-macrophage and erythroid progenitor cells were also normal, without excessive production of erythroid cells. The frequency of spleen colony-forming units (CFU-S) appeared to be strongly reduced in W/W(v) mice. The seeding fraction of RLV-infected W/W(v) stem cells in the recipient spleens did not differ from that of uninfected or RLV-infected +/+ stem cells. At equivalent numbers of CFU-S, spleen suspensions of RLV-infected W/W(v) mice were equally effective as +/+ control suspensions in protecting irradiated mice from death due to bone marrow failure. Thus the number of CFU-S observed appeared to be predictive for the number of W/W(v) cells required for effective radioprotection. In irradiated W/W(v) mice that received transplants of RLV-infected W/W(v) cells, circulating erythrocyte numbers approached those of control mice; the erythrocytes were of normal size, in contrast to the macrocytic red cells of untreated W/W(v) mice. The reduced frequency of CFU-S in RLV-infected W/W(v) mice can be readily explained by a reduced self-replicating capacity, attributable to the W/W(v) genes, which was not reconstituted by infection with RLV. The data indicate a direct involvement of pluripotent stem cells upon infection with RLV.
Topics
animal cellblood and hemopoietic systemcell differentiationcolony forming uniterythropoietic stem cellin vitro studymousenonhumanpriority journalrauscher leukemia virustherapyvirus infectionanimalanimal diseasearticlebloodbone marrow cellbone marrow transplantationclonogenic assaycytologyexperimental leukemiafemalegenotypehematopoietic stem cellmacrocytic anemiamouse mutantmouse strainRauscher leukemia virusspleentransplantationwhole body radiationAnemia, MacrocyticAnimalBone Marrow CellsBone Marrow TransplantationCell DifferentiationColony-Forming Units AssayFemaleGenotypeHematopoietic Stem CellsLeukemia, ExperimentalMiceMice, Inbred C57BLMice, Inbred DBAMice, Mutant StrainsRauscher VirusSpleenSupport, Non-U.S. Gov'tWhole-Body Irradiation
TNO Identifier
229771
ISSN
00278874
Source
Journal of the National Cancer Institute, 75(2), pp. 361-368.
Pages
361-368
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