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

Abstract

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.

We thank Erik Larsson for advice and pathological examinations of mouse organs. We acknowledge the Transgenic Mouse Facility at the Uppsala Biomedical Centre for the ES cell injections.

This work was supported by grants from the Children's Cancer Foundation of Sweden, the Swedish Medical Research Council, the Swedish Cancer Society, the DBA Foundation Inc., the Ronald McDonald Fund, the Torsten and Ragnar Söderberg Fund, and Uppsala University.