Mice with ribosomal protein S19 deficiency develop bone marrow failure and symptoms like patients with Diamond-Blackfan anemia.

Summary, in English

Diamond-Blackfan anemia (DBA) is a congenital erythroid hypoplasia caused by a functional haploinsufficiency of genes encoding for ribosomal proteins. Among these genes, ribosomal protein S19 (RPS19) is mutated most frequently. Generation of animal models for diseases like DBA is challenging since the phenotype is highly dependent on the level of RPS19 downregulation. We report the generation of mouse models for RPS19-deficient DBA using transgenic RNA interference that allows an inducible and graded downregulation of Rps19. Rps19-deficient mice develop a macrocytic anemia together with leukocytopenia and variable platelet count that with time leads to the exhaustion of hematopoietic stem cells and bone marrow failure. Both RPS19 gene transfer and the loss of p53 rescue the DBA phenotype implying the potential of the models for testing novel therapies. This study demonstrates the feasibility of transgenic RNA interference to generate mouse models for human diseases caused by haploinsufficient expression of a gene.

• Författare: Pekka Jaako; Johan Flygare; Karin Olsson; Ronan Quere; Mats Ehinger; Adrianna Henson; Steven Ellis; Axel Schambach; Christopher Baum; Johan Richter; Jonas Larsson; David Bryder; Stefan Karlsson
• Avdelning/ar: Avdelningen för molekylärmedicin och genterapi; Institutionen för experimentell medicinsk vetenskap; Tumörmikromiljö; Hematopoes och genterapi; StemTherapy: National Initiative on Stem Cells for Regenerative Therapy
• Publiceringsår: 2011
• Språk: Engelska
• Sidor: 6087-6096
• Publikation/Tidskrift/Serie: Blood
• Volym: 118
• Länkar: http://www.ncbi.nlm.nih.gov/pubmed/21989989?dopt=Abstract; http://dx.doi.org/10.1182/blood-2011-08-371963
• Dokumenttyp: Artikel i tidskrift
• Förlag: American Society of Hematology
• Ämne: Hematology
• Status: Published
• Forskningsgrupp: Hematopoiesis and Gene Therapy
• ISBN/ISSN/Övrigt: ISSN: 1528-0020