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Establishment of permanent chimerism in a lactate dehydrogenase-deficient mouse mutant with hemolytic anemia

Journal Article · · Exp. Hematol.; (United States)
OSTI ID:5719844
;
Pluripotent hemopoietic stem cell function was investigated in the homozygous muscle type lactate dehydrogenase (LDH-A) mutant mouse using bone marrow transplantation experiments. Hemopoietic tissues of LDH-A mutants showed a marked decreased in enzyme activity that was associated with severe hemolytic anemia. This condition proved to be transplantable into wild type mice (+/+) through total body irradiation (TBI) at a lethal dose of 8.0 Gy followed by engraftment of mutant bone marrow cells. Since the mutants are extremely radiosensitive (lethal dose50/30 4.4 Gy vs 7.3 Gy in +/+ mice), 8.0-Gy TBI followed by injection of even high numbers of normal bone marrow cells did not prevent death within 5-6 days. After a nonlethal dose of 4.0 Gy and grafting of normal bone marrow cells, a transient chimerism showing peripheral blood characteristics of the wild type was produced that returned to the mutant condition within 12 weeks. The transfusion of wild type red blood cells prior to and following 8.0-Gy TBI and reconstitution with wild type bone marrow cells prevented the early death of the mutants and permanent chimerism was achieved. The chimeras showed all hematological parameters of wild type mice, and radiosensitivity returned to normal. It is concluded that the mutant pluripotent stem cells are functionally comparable to normal stem cells, emphasizing the significance of this mouse model for studies of stem cell regulation.
Research Organization:
Gesellschaft fuer Strahlen- und Umweltforschung, Muenchen, Germany, F.R.
OSTI ID:
5719844
Journal Information:
Exp. Hematol.; (United States), Journal Name: Exp. Hematol.; (United States) Vol. 15:11; ISSN EXHMA
Country of Publication:
United States
Language:
English

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Related Subjects

560152* -- Radiation Effects on Animals-- Animals
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANEMIAS
ANIMAL CELLS
ANIMALS
BIOLOGICAL FUNCTIONS
BIOLOGICAL MATERIALS
BIOLOGICAL MODELS
BLOOD
BLOOD CELLS
BODY FLUIDS
BONE MARROW CELLS
CHIMERAS
CONNECTIVE TISSUE CELLS
DISEASES
ENZYME ACTIVITY
ENZYMES
ERYTHROCYTES
EXTERNAL IRRADIATION
FUNCTIONS
HEMIACETAL DEHYDROGENASES
HEMIC DISEASES
IRRADIATION
LACTATE DEHYDROGENASE
LETHAL IRRADIATION
MAMMALS
MATERIALS
MICE
MOSAICISM
MUTANTS
OXIDOREDUCTASES
RADIATION CHIMERAS
RADIOSENSITIVITY
RETICULOCYTES
RODENTS
SOMATIC CELLS
STEM CELLS
SYMPTOMS
TRANSPLANTS
VERTEBRATES
WHOLE-BODY IRRADIATION