This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Matsson, H. Articles by Dahl, N. Search for Related Content PubMed PubMed Citation Articles by Matsson, H. Articles by Dahl, N.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, May 2004, p. 4032-4037, Vol. 24, No. 9
0270-7306/04/$08.00+0     DOI: 10.1128/MCB.24.9.4032-4037.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Targeted Disruption of the Ribosomal Protein S19 Gene Is Lethal Prior to Implantation

Department of Genetics and Pathology, The Rudbeck Laboratory,¹ Department of Medical Biochemistry and Microbiology, Uppsala Biomedical Centre, Uppsala University, 751 85 Uppsala,³ Department of Molecular Medicine and Gene Therapy, Lund University, 221 84 Lund, Sweden²

Received 17 November 2003/ Accepted 31 January 2004

The ribosomal protein S19 (RPS19) is located in the small (40S) subunit and is one of 79 ribosomal proteins. The gene encoding RPS19 is mutated in approximately 25% of patients with Diamond-Blackfan anemia, which is a rare congenital erythroblastopenia. Affected individuals present with decreased numbers or the absence of erythroid precursors in the bone marrow, and associated malformations of various organs are common. We produced C57BL/6J mice with a targeted disruption of murine Rps19 to study its role in erythropoiesis and development. Mice homozygous for the disrupted Rps19 were not identified as early as the blastocyst stage, indicating a lethal effect. In contrast, mice heterozygous for the disrupted Rps19 allele have normal growth and organ development, including that of the hematopoietic system. Our findings indicate that zygotes which are Rps19^–/– do not form blastocysts, whereas one normal Rps19 allele in C57BL/6J mice is sufficient to maintain normal ribosomal and possibly extraribosomal functions.

This article has been cited by other articles:

• Uechi, T., Nakajima, Y., Chakraborty, A., Torihara, H., Higa, S., Kenmochi, N. (2008). Deficiency of ribosomal protein S19 during early embryogenesis leads to reduction of erythrocytes in a zebrafish model of Diamond-Blackfan anemia. Hum Mol Genet 17: 3204-3211 [Abstract] [Full Text]  
• Robledo, S., Idol, R. A., Crimmins, D. L., Ladenson, J. H., Mason, P. J., Bessler, M. (2008). The role of human ribosomal proteins in the maturation of rRNA and ribosome production. RNA 14: 1918-1929 [Abstract] [Full Text]  
• Pederson, T. (2007). Ribosomal protein mutations in Diamond-Blackfan anemia: might they operate upstream from protein synthesis?. FASEB J. 21: 3442-3445 [Abstract] [Full Text]  
• Gregory, L. A., Aguissa-Toure, A.-H., Pinaud, N., Legrand, P., Gleizes, P.-E., Fribourg, S. (2007). Molecular basis of Diamond Blackfan anemia: structure and function analysis of RPS19. Nucleic Acids Res 35: 5913-5921 [Abstract] [Full Text]  
• Angelini, M., Cannata, S., Mercaldo, V., Gibello, L., Santoro, C., Dianzani, I., Loreni, F. (2007). Missense mutations associated with Diamond-Blackfan anemia affect the assembly of ribosomal protein S19 into the ribosome. Hum Mol Genet 16: 1720-1727 [Abstract] [Full Text]  
• Flygare, J., Karlsson, S. (2007). Diamond-Blackfan anemia: erythropoiesis lost in translation. Blood 109: 3152-3154 [Abstract] [Full Text]  
• Adachi, K., Soeta-Saneyoshi, C., Sagara, H., Iwakura, Y. (2007). Crucial Role of Bysl in Mammalian Preimplantation Development as an Integral Factor for 40S Ribosome Biogenesis. Mol. Cell. Biol. 27: 2202-2214 [Abstract] [Full Text]  
• Roh, S. G., Kuno, M., Hishikawa, D., Hong, Y. H., Katoh, K., Obara, Y., Hidari, H., Sasaki, S. (2007). Identification of differentially expressed transcripts in bovine rumen and abomasum using a differential display method. J ANIM SCI 85: 395-403 [Abstract] [Full Text]  
• Choesmel, V., Bacqueville, D., Rouquette, J., Noaillac-Depeyre, J., Fribourg, S., Cretien, A., Leblanc, T., Tchernia, G., Da Costa, L., Gleizes, P.-E. (2007). Impaired ribosome biogenesis in Diamond-Blackfan anemia. Blood 109: 1275-1283 [Abstract] [Full Text]  
• Zhang, S., Shi, M., Hui, C.-c., Rommens, J. M. (2006). Loss of the Mouse Ortholog of the Shwachman-Diamond Syndrome Gene (Sbds) Results in Early Embryonic Lethality.. Mol. Cell. Biol. 26: 6656-6663 [Abstract] [Full Text]  
• Leger-Silvestre, I., Caffrey, J. M., Dawaliby, R., Alvarez-Arias, D. A., Gas, N., Bertolone, S. J., Gleizes, P.-E., Ellis, S. R. (2005). Specific Role for Yeast Homologs of the Diamond Blackfan Anemia-associated Rps19 Protein in Ribosome Synthesis. J. Biol. Chem. 280: 38177-38185 [Abstract] [Full Text]  
• Coulombel, L. (2005). RPS19: pleads guilty in DBA case?. Blood 105: 4549-4550 [Full Text]  
• Ebert, B. L., Lee, M. M., Pretz, J. L., Subramanian, A., Mak, R., Golub, T. R., Sieff, C. A. (2005). An RNA interference model of RPS19 deficiency in Diamond-Blackfan anemia recapitulates defective hematopoiesis and rescue by dexamethasone: identification of dexamethasone-responsive genes by microarray. Blood 105: 4620-4626 [Abstract] [Full Text]  
• Flygare, J., Kiefer, T., Miyake, K., Utsugisawa, T., Hamaguchi, I., Da Costa, L., Richter, J., Davey, E. J., Matsson, H., Dahl, N., Wiznerowicz, M., Trono, D., Karlsson, S. (2005). Deficiency of ribosomal protein S19 in CD34+ cells generated by siRNA blocks erythroid development and mimics defects seen in Diamond-Blackfan anemia. Blood 105: 4627-4634 [Abstract] [Full Text]  
• Dai, M.-S., Lu, H. (2004). Inhibition of MDM2-mediated p53 Ubiquitination and Degradation by Ribosomal Protein L5. J. Biol. Chem. 279: 44475-44482 [Abstract] [Full Text]  
• Bagby, G. C., Lipton, J. M., Sloand, E. M., Schiffer, C. A. (2004). Marrow Failure. ASH Education Book 2004: 318-336 [Abstract] [Full Text]