ArticleDisease models & mechanisms2022
Limitations of mouse models for sickle cell disease conferred by their human globin transgene configurations.
Article in Disease models & mechanisms, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 21 citations in OpenAlex.
- Daprodustat augments red cell and γ-globin production in models of sickle cell disease.Blood red cells & iron · 2026Article
- Ferroportin inhibition attenuates pulmonary hypertension in hypoxic sickle cell disease mice.Blood advances · 2026Article
- In situ gene editing of hematopoietic stem cells via AAV-delivered CRISPR guide RNAs.Blood advances · 2025Article
- Selective AMPKβ1 activation induces fetal hemoglobin in human erythroid cells and sickle cell mice via the noncanonical NRF2 pathway.Science advances · 2025Article
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- Challenges and opportunities for conceiving genetically diverse sickle cell mice.Trends in molecular medicine · 2025Review
- Reduced GATA1 levels are associated with ineffective erythropoiesis in sickle cell anemia.Haematologica · 2025Article
- From early development to maturity: a phenotypic analysis of the Townes sickle cell disease mice.Biology open · 2025Article
- Total ginsenosides enhance γ-globin expression and fetal hemoglobin production in β-thalassemia models.Frontiers in pharmacology · 2025Article
- Transcriptional regulators of fetal hemoglobin.Hematology, transfusion and cell therapy · 2024Review
- CRISPR technology in human diseases.MedComm · 2024Review
- A novel high-titer, bifunctional lentiviral vector for autologous hematopoietic stem cell gene therapy of sickle cell disease.Molecular therapy. Methods & clinical development · 2024Article
- Mouse models of sickle cell disease: Imperfect and yet very informative.Blood cells, molecules & diseases · 2024Review
- Multi-Organ Morphological Findings in a Humanized Murine Model of Sickle Cell Trait.International journal of molecular sciences · 2023Article
- Engineering of the endogenouseLife · 2023Article
- The BACH1 inhibitor ASP8731 inhibits inflammation and vaso-occlusion and induces fetal hemoglobin in sickle cell disease.Frontiers in medicine · 2023Article
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
We characterized the human β-like globin transgenes in two mouse models of sickle cell disease (SCD) and tested a genome-editing strategy to induce red blood cell fetal hemoglobin (HbF; α2γ2). Berkeley SCD mice contain four to 22 randomly arranged, fragmented copies of three human transgenes (HBA1, HBG2-HBG1-HBD-HBBS and a mini-locus control region) integrated into a single site of mouse chromosome 1. Cas9 disruption of the BCL11A repressor binding motif in the γ-globin gene (HBG1 and HBG2; HBG) promoters of Berkeley mouse hematopoietic stem cells (HSCs) caused extensive death from multiple double-strand DNA breaks. Long-range sequencing of Townes SCD mice verified that the endogenous Hbb genes were replaced by single-copy segments of human HBG1 and HBBS including proximal but not some distal gene-regulatory elements. Townes mouse HSCs were viable after Cas9 disruption of the HBG1 BCL11A binding motif but failed to induce HbF to therapeutic levels, contrasting with human HSCs. Our findings provide practical information on the genomic structures of two common mouse SCD models, illustrate their limitations for analyzing therapies to induce HbF and confirm the importance of distal DNA elements in human globin regulation. This article has an associated First Person interview with the first author of the paper.
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