A mouse model for hemoglobin SC disease recapitulates characteristic human pathologies
Sickle cell disease (SCD) is a common, life-threatening group of disorders caused by missense mutations in the β-globin gene (HBB). Mouse models have helped to elucidate the most common form of SCD (hemoglobin SS [HbSS]; homozygous p.Glu6Val) and develop new therapies. In contrast, a lack of animal models has restricted research on the second most common form of SCD (hemoglobin SC [HbSC]; p.Glu6Val/p.Glu6Lys). We used CRISPR genome engineering to generate HbSC alleles in the Townes mouse strain, which harbors human α- and β-globin genes in place of the mouse counterparts. Compared to Townes HbSS mice, HbSC mice exhibited signature pathologies that distinguish HbSC disease in humans.
Authors
- Roberta N. Rooney
- Krishnan Venkataraman
- Jonathan Yen (ORCID: https://orcid.org/0000-0002-9432-9450)
- Jahnavi Gollamudi (ORCID: https://orcid.org/0000-0003-2992-6264)
- Shondra M. Pruett‐Miller (ORCID: https://orcid.org/0000-0002-3793-585X)
- Jing Yu (ORCID: https://orcid.org/0000-0001-6311-4214)
- Michael A. Dyer
- Ali Khalighifar (ORCID: https://orcid.org/0000-0002-2949-8143)
- Patrick G. Gallagher (ORCID: https://orcid.org/0000-0002-5424-0224)
- Tam Tran
- Danielle R. Little
- James B. Papizan (ORCID: https://orcid.org/0000-0003-4257-6246)
- Jian Xu (ORCID: https://orcid.org/0000-0002-8162-889X)
- Pamela M. Martin (ORCID: https://orcid.org/0000-0001-6278-4953)
- Natalie McDonald (ORCID: https://orcid.org/0000-0002-2665-2483)
- Jinbin Zhai
- Elizabeth D. Arnold (ORCID: https://orcid.org/0009-0000-8916-667X)
- Kalin Mayberry (ORCID: https://orcid.org/0009-0002-6582-1806)
- Justina McEvoy (ORCID: https://orcid.org/0000-0003-0382-1288)
- Hieu Vu
- Ravirajsinh N. Jadeja (ORCID: https://orcid.org/0000-0002-1712-454X)
- Min Ni (ORCID: https://orcid.org/0000-0002-4587-1622)
- Laura J. Janke (ORCID: https://orcid.org/0000-0002-9871-6239)
- Yan Zheng (ORCID: https://orcid.org/0000-0001-7254-7564)
- Jingjing Zhang (ORCID: https://orcid.org/0000-0002-1349-9184)
- Yu Yao (ORCID: https://orcid.org/0000-0001-9286-4014)
- Mitchell J. Weiss (ORCID: https://orcid.org/0000-0002-6734-4858)
- Hyacinth Hyacinth
- Jaison John (ORCID: https://orcid.org/0009-0000-2825-0675)
Institutions
- Meharry Medical College (US)
- St. Jude Children's Research Hospital (US)
- Nationwide Children's Hospital (US)
- Augusta University (US)
- University of Cincinnati (US)
- University of Cincinnati Medical Center (US)
Publication Details
- Journal
- Blood Advances
- Published
- 2025-08-27
- DOI
- https://doi.org/10.1182/bloodadvances.2025016793
- Citations
- 2
- Primary Topic
- Hemoglobinopathies and Related Disorders
- Type
- article
- Field-Weighted Citation Impact
- 3.25
Funders
- American Lebanese Syrian Associated Charities
- National Institutes of Health
- National Cancer Institute