Project description:Transcriptome profile of highly purified multipotential (P), erythroid (E), and myeloid (M) bone marrow progenitors from three RPS19 mutated Diamond-Blackfan anemia and six control human subjects. Two group comparison of sex and age matched subjects. Bone marrow progenitors, gene expression profiling, Diamond-Blackfan anemia, RPS19
Project description:Gene expression analysis from erythroid progenitors (CD34+/CD71(high)/CD45- mononuclear cells from the bone marrow) of patients with Diamond-Blackfan anemia (due to RPS19 mutations) and control individuals.
Project description:Gene expression analysis from erythroid progenitors (CD34+/CD71(high)/CD45- mononuclear cells from the bone marrow) of patients with Diamond-Blackfan anemia (due to RPS19 mutations) and control individuals. Case-control microarray gene expression analysis
Project description:RPS19 mutations are the most common cause of the human disorder Diamond Blackfan Anemia. The R62W mutation was hypothesized to act in a dominant negative fashion and mice expressing RPS19R62W have many of the characteristics of Diamond Blackfan Anemia. Diamond-Blackfan Anemia (DBA), is an inherited erythroblastopenia associated with mutations in at least 8 different ribosomal protein genes. Mutations in the gene encoding Ribosomal Protein S19 (RPS19) have been identified in ~25% of DBA families. Most of these mutations disrupt either the translation or stability of the RPS19 protein and are predicted to cause DBA by haploinsufficiency. However, approximately ~30% of RPS19 mutations are missense mutations that do not alter the stability of the RPS19 protein and are hypothesized to act by a dominant negative mechanism. To formally test this hypothesis, we generated a transgenic mouse model expressing an RPS19 mutation in which an Arginine residue is replaced with a Tryptophan residue at codon 62 (RPS19R62W). Constitutive expression of RPS19R62W in developing mice was lethal. Conditional expression of RPS19R62W resulted in growth retardation, a mild anemia with reduced numbers of erythroid progenitors and significant inhibition of terminal erythroid maturation, similar to DBA. RNA profiling demonstrated over 700 dysregulated genes belonging to the same pathways that are disrupted in RNA profiles of DBA patient cells.
Project description:Transcriptome profile of highly purified multipotential (P), erythroid (E), and myeloid (M) bone marrow progenitors from three RPS19 mutated Diamond-Blackfan anemia and six control human subjects.
