Effect of Kcc1 activation in sickle cell disease. (A) Hematocrits of 10-week-old mice. Mean ± SD of ≥5 mice for each genotype except Hb^SSKcc1^M935K/M935K, which was a single animal. *P < .05 compared with Kcc1^+/+. (B) Percent reticulocytes in peripheral blood measured by thiazole orange. Mean ± SD of ≥3 mice for each genotype. *P < .05 compared with sickle homozygous (SS) Kcc1^+/+. (C) Representative spleens from 10-week-old mice with the stated genotypes. (D) Survival curves of homozygous sickle mice that are wild-type (+/+), heterozygous (+/m), or homozygous (m/m) for Kcc1^M935K. P values compared with Kcc1^+/+ mice were calculated using the log-rank (Mantel-Cox) test. (E) ⁸⁶Rb efflux from red cells of transgenic mice expressing wild-type adult human β-globin (AA), heterozygous for sickle cell mutation (AS), or homozygous for sickle cell mutation (SS) that are wild type (+/+), heterozygous (+/m), or homozygous (m/m) for Kcc1^M935K. *P < .05 compared with Kcc1^+/+. (F) Effect of heterozygous Kcc1^M935K (+/m) on red cell densities of wild-type (AA), and heterozygous sickle (AS) mice determined by centrifugation through Percoll mixture of defined density. Student t test: AS^+/m compared with AS^+/+, *P < .05.