These mice harbor several mutations:
1) the Tg(LCRHBA1,LCRHBB)1Tow mutation (also called Hb S) designed with expression of the human hemoglobin beta chain complex (HBB) and human α1 globin (HBA1) being controlled independently by five upstream sites (HS I-V) of the human β-globin locus control regions (LCR). The HS I-V betaS transgene expresses a glutamic acid to valine mutation of the human hemoglobin beta chain complex (HBB) that has been linked to Sickle Cell Disease.
as well as
2) the Hbbd3th mutation (also called βmajor) containing a spontaneous deletion of endogenous Hbb gene.
Hb S mice were bred to Hbbd3th mice to increase expression of human β-globins in Hb S/β-thal mice. Hb S and Hb S/β-thal mice contain three and five times the level of endogenous mouse β-globin mRNA, respectively. They contain equivalent amounts of human α- and endogenous mouse α-globin mRNA. The donating investigator maintains the Hb S/β-thal mice by breeding mice heterozygous for the β-thal mutation and carrying one transgene copy. Mice homozygous for the β-thal mutation and homozygous for the transgene are viable.
Both groups exhibit decreased red blood cell counts and Hb concentrations. Reticulocyte counts are increased in Hb S/β-thal mice, indicating that they are mildly anemic. The spleens of Hb S/β-thal mice are two to four times larger than control spleens, as seen in children with sickle cell disease. Hypoxia (5% O2), causes the percentage of circulating sickled cells in the blood to increase, and leads to death from sickling-dependent pulmonary sequestration within 15 minutes.
