title: Establishing Rps6 hemizygous mice as a model for studying how ribosomal protein haploinsufficiency impairs erythropoiesis.
abstract: Diamond-Blackfan anemia is a congenital hypoproliferative macrocytic anemia and 5q- syndrome myelodysplastic syndrome is an acquired hypoproliferative macrocytic anemia. Their common erythroid phenotype reflects a shared pathophysiology-haploinsufficiency of one of many ribosomal proteins and somatic deletion of one allele of the ribosomal protein S14 gene, respectively. Although these abnormalities lead to defective ribosome biogenesis, why ribosomal protein hemizygosity results in anemia is not certain. Here, we characterize the hematopoietic phenotype of mice lacking one allele of the ribosomal protein S6 gene. The mice have an erythroid phenotype similar to both Diamond-Blackfan anemia and the 5q- syndrome and lenalidomide therapy improves their anemia.
authors.affiliation: Department of Medicine, University of Washington, Seattle, WA 98195-7710, USA.
authors.forename: Siobán B
authors.initials: SB
authors.lastname: Keel
authors.forename: Susan
authors.initials: S
authors.lastname: Phelps
authors.forename: Kathleen M
authors.initials: KM
authors.lastname: Sabo
authors.forename: Monique N
authors.initials: MN
authors.lastname: O'Leary
authors.forename: Catherine B
authors.initials: CB
authors.lastname: Kirn-Safran
authors.forename: Janis L
authors.initials: JL
authors.lastname: Abkowitz
mesh_terms: D000380:Agranulocytosis / Q000235:genetics; D000483:Alleles; D029503:Anemia, Diamond-Blackfan / Q000097:blood / Q000235:genetics; D000748:Anemia, Macrocytic / Q000097:blood / Q000188:drug therapy / Q000209:etiology / Q000235:genetics*; D000818:Animals; D002872:Chromosome Deletion; D002895:Chromosomes, Human, Pair 5 / Q000235:genetics; D004195:Disease Models, Animal; D004909:Erythrocyte Indices / Q000187:drug effects; D004920:Erythropoiesis / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental; D006454:Hemoglobins / Q000032:analysis; D006579:Heterozygote; D000077269:Lenalidomide; D008231:Lymphopenia / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D011241:Prednisone / Q000627:therapeutic use; D016601:RNA-Binding Proteins / Q000235:genetics; D038601:Ribosomal Protein S6 / Q000172:deficiency / Q000235:genetics*; D012269:Ribosomal Proteins / Q000172:deficiency / Q000235:genetics; D012270:Ribosomes / Q000502:physiology; D013792:Thalidomide / Q000031:analogs & derivatives / Q000627:therapeutic use; D013922:Thrombocytosis / Q000235:genetics
chemical_list: D006454:Hemoglobins; D016601:RNA-Binding Proteins; C522051:RPL22 protein, mouse; D038601:Ribosomal Protein S6; D012269:Ribosomal Proteins; C084343:Rpl29 protein, mouse; C448579:ribosomal protein S6, mouse; D013792:Thalidomide; D000077269:Lenalidomide; D011241:Prednisone