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

Journal Article · Tue Dec 01 00:00:00 EST 1987 · Exp. Hematol.; (United States)

OSTI ID:5719844

Datta, T; Doermer, P

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), Vol. 15:11
• Country of Publication: United States
• Language: English

Related Subjects

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