Faculty Research 1990 - 1999

Title

Hematopoietic repopulation of adult mice with beta-thalassemia.

Document Type

Article

Publication Date

1994

Keywords

Animal, Bone-Marrow-Transplantation, Erythrocyte-Count, Female, Hematopoiesis, Male, Mice, Mice-Inbred-C57BL, Mice-Inbred-DBA, Mutation, Radiation-Dosage, SUPPORT-U-S-GOVT-P-H-S

JAX Source

Blood 1994 Feb 1;83(3):828-32

Grant

DK27726/DK/NIDDK

Abstract

Deletion of the murine beta-major globin gene on chromosome 7 causes a severe, hypochromic anemia in homozygous mice. We show that over 50% of the homozygous mice die either in utero or at birth. Mice heterozygous for the deletion have a slightly increased percentage of reticulocytes when compared with normal mice, but no clinical anemia. As a therapeutic measure, we transplanted 2 x 10(6) congenic genetically marked normal (+/+) marrow cells into adult homozygous and control heterozygous mice. Pretreatment with marrow ablative irradiation was required to obtain significant percentages of donor peripheral blood cells in the homozygous mice. Red blood cell (RBC) counts normalized after pretransplantation irradiation of thalassemic mice with nonlethal doses as low as 400 R. The thalassemic mice irradiated with 200, 400, and 600 R were erythroid-cell chimeras and remained so for at least 8 months posttransplantation, whereas those irradiated with 800 R had primarily donor erythrocytes by 8 weeks. RBC replacement preceded non-erythroid cell replacement at 200, 400, and 600 R. This selective repopulation was more noticeable in the thalassemic mice than in control mice. The fact that chimeric mice are cured, coupled with a recent observation by others that erythroid replacement occurs in unirradiated newborn thalassemic mice, suggest transplantation therapy in utero might augment survival.