Diamond-Blackfan Anemia (DBA) Animal Model Service

The lack of animal models that faithfully recapitulate the erythroid-specific defects and genetic heterogeneity of Diamond-Blackfan anemia (DBA) remains a major bottleneck in translational research. At Protheragen, we specialize in developing highly precise animal models to accelerate preclinical research for potential DBA therapies. Our expertise ensures that clients receive the most reliable and physiologically relevant models, ultimately streamlining their drug development pipeline.

Introduction to Diamond-Blackfan Anemia (DBA) Animal Models

Animal models used to study Diamond-Blackfan anemia (DBA) are important preclinical tools designed to mimic the hallmark feature of this inherited bone marrow failure syndrome: erythroid developmental disorders. These models are primarily constructed by targeting mutations or deletions in ribosomal protein genes, such as Rps19, Rps24, or Rpl5. These gene mutations or deletions correspond to the most common genetic abnormalities in human DBA patients, thus these models faithfully represent key pathological features. This high phenotypic fidelity makes them an indispensable system for studying the mechanisms linking ribosomal dysfunction to specific erythroid defects, understanding differences in disease penetrance, and evaluating novel treatment strategies.

Fig.1 Zebrafish models of Diamond-Blackfan anemia (DBA). (Uechi T, Kenmochi N., 2019)

Our Services

Leveraging advanced genetic engineering and a deeply experienced scientific team, Protheragen delivers comprehensive animal model development services for Diamond-Blackfan anemia (DBA) research, accelerating the discovery of therapeutic solutions for this rare inherited anemia. Our rigorously validated models faithfully recapitulate core disease hallmarks, including profound erythroid failure, macrocytic anemia, and developmental anomalies, establishing them as indispensable tools for elucidating pathogenic mechanisms, validating novel drug targets, and assessing the efficacy of promising therapeutic candidates.

Animal Models of Diamond-Blackfan Anemia (DBA)

Genetically Engineered Models

• Rps19 Knockout Models
• Rps19 Mutation Models
• Rps19 Knockdown Models

• Rps6 Conditional Knockout Models
• Rpl24 Mutation Models
• Other Models

Patient-Derived Xenograft (PDX) Models

At Protheragen, our scientists constructed PDX models by transplanting human CD34+ hematopoietic stem/progenitor cells from patients with RPS19 haploid deficiency into NOD/SCID immunodeficient mice. These models clearly demonstrate that RPS19 deficiency is the pathogenic mechanism of DBA erythroid deficiency and lay the foundation for evaluating gene therapy strategies for this disease.

Featured Animal Models

Case Study-Rpl11 Haploinsufficiency Mouse Model (Rpl11^+/Δ)

Model Introduction

To address the critical need for representative animal models in Diamond-Blackfan anemia (DBA) research, Protheragen has successfully generated a novel, inducible mouse model. This model is engineered for conditional haploinsufficiency of the Rpl11 gene, a ribosomal protein gene frequently mutated in human DBA. This innovative model recapitulates the severe macrocytic anemia and disease progression observed in DBA patients, providing a powerful tool for preclinical investigation.

Methodology

• Animal Model: Mx1-Cre Rpl11^+/flox experimental mice were generated by cross-breeding homozygous Rpl11^flox/flox and Mx1-cre breeders. Haploinsufficiency of Rpl11 (Rpl11^+/Δ) was induced by intraperitoneal injection of polyinosinic-polycytidylic acid to mice with Mx1-Cre Rpl11^+/flox on postnatal day 8 and 10. The experimental cohort consisted of Rpl11^+/Δ mice and their wild-type (WT) littermate controls.
• Phenotypic Analysis Methods:
  • Hematological Analysis: Hematological profiling was performed by measuring hemoglobin (Hb) levels and mean corpuscular volume (MCV) to determine anemia severity and type, alongside white blood cell (WBC) and platelet (PLT) counts to investigate systemic compensatory responses.
  • Survival Analysis: Mice were monitored longitudinally to assess the lethality of the anemia and determine median survival.

Phenotypic Analysis & Results

The Rpl11^+/Δ mice exhibited a rapid and lethal phenotype, closely recapitulating the core hallmarks of Diamond-Blackfan anemia (DBA). The results are categorized as follows:

• Onset of Severe Macrocytic Anemia: Compared to WT controls, Rpl11^+/Δ mice developed severe macrocytic anemia within two weeks post-induction, characterized by a significant drop in hemoglobin (Hb) levels (Hb < 10 g/dL).
• Dysregulation of Other Hematopoietic Lineages: Analysis revealed significant elevations in mean corpuscular hemoglobin (MCH) and platelet (PLT) counts in Rpl11^+/Δ mice compared to WT, suggesting potential compensatory hematopoietic responses. In contrast, white blood cell (WBC) counts, while tending to be lower, showed no statistically significant difference compared to WT controls (Fig.2A).
• Progressive Lethality: The anemia was progressive and ultimately fatal. All Rpl11^+/Δ mice succumbed to severe anemia (Hb < 2 g/dL) by 30 weeks of age, with a highly significant median survival of only 27 weeks (Fig.2B).

Fig.2 Phenotypic characterization of Rpl11^+/Δ mice. (A) Comparison of key hematological parameters: hemoglobin (Hb), mean corpuscular volume (MCV), white blood cell (WBC), and platelet (PLT) counts between Rpl11^+/Δ and wild-type (WT) mice. (B) Survival curve comparing Rpl11^+/Δ and WT mice. Data are presented as mean ± SEM (n=7). ***p < 0.001 vs. WT.

Conclusion

This case study validates the Rpl11 haploinsufficiency mouse as a robust model for severe Diamond-Blackfan anemia (DBA). The model successfully recapitulates critical disease hallmarks, including rapid-onset macrocytic anemia, dysregulated hematopoiesis, and progressive lethality due to bone marrow failure. This makes it an ideal and reliable preclinical platform for investigating DBA disease mechanisms and evaluating the efficacy of novel therapeutic strategies.

Contact Us

Specializing in preclinical drug development solutions, Protheragen offers comprehensive animal models to advance pharmacodynamics (PD), pharmacokinetics (PK), and toxicology studies, thereby supporting the development and regulatory approval of potential therapies. If you are interested in our animal model development services, please do not hesitate to contact us for more details and quotation information.

Reference

• Uechi T, Kenmochi N. Zebrafish models of diamond-blackfan anemia: a tool for understanding the disease pathogenesis and drug discovery[J]. Pharmaceuticals, 2019, 12(4): 151.