Osmotic deformability and fragility curves for RBCs from Tmod1-null mice are consistent with mild spherocytic elliptocytosis. (A) Representative osmotic deformability curves measured by ektacytometry for RBCs from Tmod1^+/+Tg+ mice and (B) from Tmod1^−/−Tg+ mice, showing decreased deformability with a double-humped peak characteristic of elliptocytosis.⁴³  (C) The maximum deformability, DI_max, a direct measure of the ability of the cells to deform under isotonic conditions, is reduced approximately 17% for Tmod1-null RBCs, from 0.481 to 0.402. (D) The osmolality at which cells are least deformable under hypotonic conditions, O_min, is a measure of the surface area-to-volume ratio and corresponds to the osmolality at which 50% of cells lyse in a standard osmotic fragility test; O_min is increased in Tmod1-null RBCs. (E) The osmolality at which cells exhibit half-maximal deformability under hypertonic conditions is affected by both mechanical properties of the membrane and hemoglobin concentration.²⁹  The slight increase for Tmod1-null RBCs, with an increase in mean corpuscular Hbg concentration (Table 1) is consistent with modestly weakened mechanical properties of the membrane. (F) The osmotic fragility curve shows a small rightward shift for Tmod1-null RBCs, confirming the shift in O_min. (G) The osmolality at which 50% of RBCs are lysed is increased significantly for Tmod1-null RBCs. Nine (A-E) and 6 (F-G) mice of each genotype (Tmod1^+/+Tg+ and Tmod1^−/−Tg+). ***P < .001; **P < .01; *P < .05.