2026/01/01 by Juraj Kokavec, Tereza Turková, Björn Schuster +11 · 1 voice
Biochemistry, Genetics and Molecular Biology · #RNA modifications and cancer #RNA and protein synthesis mechanisms #Epigenetics and DNA Methylation
paper · pdf · doi:10.1002/hem3.70302
openalex publication_date 2026/01/01 · openalex created_date 2026/01/20 · openalex updated_date 2026/07/22
Abstract Diamond–Blackfan anemia (DBA) is a rare bone marrow failure syndrome accompanied by cardiovascular, skeletal, and urogenital abnormalities. Most of the affected individuals carry mutations in ribosomal proteins, including RPS19, a component of the 40S ribosomal subunit. We developed a transgenic Rps19 mouse model harboring a deletion of conserved R67 that displays a variable phenotype ranging from mild hematopoietic defects to severe anemia and a set of other skeletal, muscular, and cardiac abnormalities with shorter survival. This mouse model exhibited an activation of the p53 signaling pathway in red blood cell committed hematopoietic stem and progenitor cells, affecting erythroid lineage development. Competitive transplantation assays using Rps19 R67∆ bone marrow progenitor cells confirmed that short‐term repopulating hematopoietic stem cells (HSCs) and their progenitor lineages were affected, while their differentiation was rescued after deletion of the tumor suppressor Trp53 . Rps19 R67∆ mutation leads to pre‐ribosomal RNA (pre‐rRNA) accumulation coupled with activation of p53, even at relatively immature hematopoietic stages. In conclusion, we present a mouse model that represents a powerful tool for exploring new therapeutic options for the treatment of ribosomal disorders, including DBA.