title: The hemoglobin-deficit mouse: analysis of phenotype and hematopoiesis in the transplant model.
abstract: The mouse mutant hemoglobin deficit (gene symbol hbd) is characterized by a severe microcytic anemia that is inherited in an autosomal-recessive manner. To assess the mutation's effect on hematopoiesis, unfractionated bone marrow (BM) from either a mutant C57BL6/J-hbd/hbd, Gpi1b/Gpi1b (phenotype symbol HBD), or normal C57BL6/J-+hbd/+hbd, Gpi1b/Gpi1b mouse was injected intravenously into irradiated congenic C57BL6/J-+hbd/+hbd, Gpi1a/Gpi1a, lgh(a)/lgh(a), Thy1a/Thy1a mice. The congenic recipients of mutant or normal marrow obtained complete red blood cell (RBC) and leukocyte reconstitution, with the exception of one recipient of HBD marrow. After 24 weeks posttransplantation, the normal recipients of HBD marrow obtained a microcytic anemia similar to the donor. These results suggest that the HBD phenotype is caused by a BM defect. We observed that the erythroid lineage derived from donor HBD marrow repopulated more slowly than the normal marrow at 4 weeks post-transplantation. To determine if this difference was 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 contribution 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 assays were performed: absolute numbers of bone progenitors were increased, suggesting that the defect results in a late block to erythroid differentiation.
authors.affiliation: National Heart, Lung, and Blood Institute, Bethesda, MD 20892, USA.
authors.forename: M L
authors.initials: ML
authors.lastname: Bloom
authors.forename: K L
authors.initials: KL
authors.lastname: Simon-Stoos
mesh_terms: D000818:Animals; D016026:Bone Marrow Transplantation; D017690:Cell Transplantation; D006410:Hematopoiesis / Q000235:genetics*; D006454:Hemoglobins / Q000172:deficiency* / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008817:Mice, Mutant Strains
chemical_list: D006454:Hemoglobins