THE HEMOGLOBIN-DEFICIT MOUSE - ANALYSIS OF PHENOTYPE AND HEMATOPOIESIS IN THE TRANSPLANT MODEL

The mouse mutant hemoglobin deficit (gene symbol hbd) is characterized by a severe microcytic anemia that is inherited in an autosomal-reces sive manner. To assess the mutation's effect on hematopoiesis, unfract ionated bone marrow (BM) from either a mutant: C57BL6/J-hbd/hbd, Gpi1( b)/Gpi1(b) (phenotype symbol HBD), or normal C57BL6/J -+(hbd)/+(hbd), Gpi1(b)/Gpi1(b) mouse was injected intravenously into irradiated conge nic C57BL6/J-+(hbd)/+(hbd), Gpi1(a)/Gpi1(a), Igh(a)/Igh(a), Thy1(a)/Th y1(a) mice, The congenic recipients of mutant or normal marrow obtaine d complete red blood cell (RBC) and leukocyte reconstitution, with the exception of one recipient of HBD marrow, After 24 weeks posttranspla ntation, the normal recipients of HBD marrow obtained a microcytic ane mia similar to the donor, These results suggest that the HBD phenotype is caused by ii SM defect, We observed that. the erythroid lineage de rived from donor HBD marrow repopulated more slowly than the normal ma rrow at 4 weeks posttransplantation. To determine if this difference w as a result of an erythropoietic defect, competitive repopulation was performed using either mutant or normal marrow competed against normal congenic marrow. For the erythroid lineage, no significant contributi on from HBD marrow was observed, To assess if the RBC block was based on a deficiency of myeloid progenitors, both in vitro and in vivo assa ys were performed: absolute numbers of bone progenitors were increased , suggesting that the defect results in a late block to erythroid diff erentiation.