A mouse model for hemoglobin SC disease recapitulates characteristic human pathologies.

Abstract

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.