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 b-globin gene (HBB). Mouse models have helped to elucidate the most common form of SCD (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 (HbSC, p.Glu6Val/p.Glu6Lys). We used CRISPR genome engineering to generate HbSC alleles in the Townes mouse strain, which harbors human a- and b-globin genes in place of the mouse counterparts. Compared to Townes HbSS mice, HbSC mice exhibited signature pathologies that distinguish HbSC disease in humans.